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Insulin is the hormone responsible for maintaining glucose homeostasis in the body, in addition to participating in lipid metabolism, protein synthesis, and the inhibition of gluconeogenesis. These functions are well characterized in the classic organ target cells that are responsible for general energy regulation: the liver, skeletal muscle, and adipose tissue. However, these actions are not restricted to these tissues because insulin has been shown to affect most cells in the body. This review describes the role of insulin in leukocyte signaling pathways, metabolism and functions, and how insulin resistance could affect this signaling and deteriorate leukocyte metabolism and function, in addition to showing evidence that suggests leukocytes may substantially contribute to the development of systemic insulin resistance.

Background: handgrip strength (HGS) is a health-status parameter associated with multicomorbidity in the adult population. Objective: the aim of the present study was to determine the association between HGS (i.e., absolute and relative) and abdominal obesity (AO), type-2 diabetes (T2D), and hypertension (HT), as well as to determine the association between low relative HGS with the presence of multicomorbidity (i.e., the co-occurrence of two or more comorbidities together) in a Mexican population. Methodology: a cross-sectional study was carried out in 860 participants from the south of Mexico (661 women and 199 men). The age range evaluated was from 18 to 65 years. Assessments were made of sociodemographic data, clinical history, anthropometric parameters, and measurement of maximal HGS. Results: the regression models adjusted by age show that the presence of comorbidities (i.e., AO, HT and T2D) was linked negatively to HGS (i.e., absolute and relative). Moreover, in men, a low relative HGS in both hands reported an association with the presence of three simultaneous comorbidities (right, RR: 17.2, p0.001; left, RR: 11.92, p = 0.020). In women the same association was found (right, RR: 10.42, p0.001; left, RR: 9.90, p0.001). Conclusion: lower levels of relative HGS were linked to the presence of simultaneous comorbidities (i.e., the joint presence of AO, T2D and HT). Furthermore, HGS (i.e., absolute and relative) presented an inverse association with individual anthropometric and clinical parameters related to cardiovascular risk in the Mexican population.Introducción: la fuerza prensil de la mano (FPM) es un parámetro asociado con la multicomorbilidad en la población adulta. Objetivo: el objetivo del presente estudio fue determinar la asociación entre la FPM (absoluta y relativa) y la obesidad abdominal (OA), la diabetes tipo 2 (DT2) y la hipertensión (HT), así como su asociación con la multicomorbilidad (co-occurrencia de dos o más comorbilidades conjuntas) en una población mexicana. Metodología: se presenta un estudio transversal realizado en 860 participantes del sur de México (661 mujeres y 199 hombres). El rango de edad de los participantes fue de 18 a 65 años. Se evaluaron las características sociodemográficas de la población, los parámetros clínicos y antropométricos, y la medición de la FPM máxima. Resultados: los resultados demostraron una asociación entre la disminución de la FPM (absoluta y relativa) y la presencia de comorbilidades (OA, DT2 e HT). En los hombres, la disminución de la FPM relativa reportada en ambas manos se asoció con la presencia simultánea de tres comorbilidades (derecha, RR: 17,2, p0,001; izquierda, RR: 11,92, p = 0,020). Se observó una asociación similar también en las mujeres (derecha, RR: 10,42, p0,001; izquierda, RR: 9,90, p0,001). Conclusión: los bajos niveles de FPM relativa se asocian con la presencia simultánea de comorbilidades (presencia conjunta de OA, DT2 y HT). Además, la FPM (absoluta y relativa) se relaciona negativamente con los parámetros clínicos y antropométricos relacionados con el riesgo cardiovascular en la población mexicana.

Systemic lupus erythematosus (SLE) involves a broad range of factors that contribute to the development of the disease and its comorbidities. Genetic predisposition influences the developme...

Systemic sclerosis (SSc) is a rare autoimmune disease with high mortality, characterized by chronic inflammation and fibrosis, which are processes associated with higher serum tumor necrosis factor-α (sTNF-α) levels. TNFA -308G>A and -238G>A polymorphisms have been associated with higher sTNF-α levels. In this study, we genotyped the TNFA -308G>A and -238G>A polymorphisms in 53 SSc patients and 115 unrelated control subjects (CS) from southern Mexico. The TNFA mRNA expression and sTNF-α levels were also quantified by qPCR and enzyme-linked immunosorbent assays, respectively. TNFA -308GA genotype was associated with disease susceptibility according to a codominant genetic model (OR = 3.2, 95% CI 1.05–9.75, p = 0.03), and with higher anti-fibrillarin antibodies (p = 0.01), and higher skin thickening (p = 0.006). TNFA -238GA was not associated with SSc risk. TNFA mRNA expression and sTNF-α levels were similar between SSc patients and CS and were not statistically associated with the TNFA polymorphisms; however, a correlation (rho = 0.362, p = 0.009) between sTNF-α levels with anti-RNA polymerase III antibodies was observed in the SSc patients. In conclusion, the -308G>A polymorphism is a genetic marker of SSc susceptibility in population from southern Mexico, and it is associated with skin thickening and anti-fibrillarin antibodies. In addition, sTNF-α levels correlate positively with the anti-RNA pol III antibodies levels.

The enzymes of the family peptidylarginine deiminases (PADs) have an important role in the pathogenesis of rheumatoid arthritis (RA) due to their association with the anti-citrullinated protein antibodies (ACPA) production. To evaluate the association between single-nucleotide polymorphisms (SNPs) in the PADI2 gene and RA susceptibility, related clinical parameters, and the serologic status of autoantibodies in a women population with RA from southern Mexico, a case-control study was conducted (case n=229; control n=333). Sociodemographic characteristics were evaluated, along with clinical parameters, inflammation markers, the levels of ACPAs as anti-cyclic citrullinated peptides (anti-CCPs), anti-modified citrullinated vimentin (anti-MCV), and rheumatoid factor (RF). Genomic DNA was extracted from peripheral blood, and three SNPs of the PADI2 gene (rs1005753, rs2057094, and rs2235926) were performed by qPCR using TaqMan probes. The data analysis reveals that the carriers of the T allele for rs2057094 and rs2235926 presented an earlier onset of the disease (β= -3.26; p = 0.03 and β = -4.13; p = 0.015, respectively) while the carriers of the T allele for rs1005753 presented higher levels of anti-CCPs (β= 68.3; p = 0.015). Additionally, the T allele of rs2235926 was associated with a positive RF (OR = 2.90; p = 0.04), anti-MCV (OR = 2.92; p = 0.05), and with the serologic status anti-CCP+/anti-MCV+ (OR = 3.02; p = 0.03), and anti-CCP+/anti-MCV+/RF+ (OR = 3.79; p = 0.004). The haplotypes GTT (OR =1.52; p = 0.027) and TTT (OR = 1.32; p = 0.025) were associated with the presence of RA. In addition, in this study the haplotype TTT is linked to the presence of radiographic joint damage defined by a Sharp-van der Heijde score (SHS) ≥2 (OR = 1.97; p = 0.0021) and SHS ≥3 (OR = 1.94; p = 0.011). The haplotype TTT of SNPs rs1005753, rs2057094, and rs2235926 of the PADI2 gene confers genetic susceptibility to RA and radiographic joint damage in women from southern Mexico. The evidence reveals that SNPs of the PADI2 gene favors the presence of a positive serologic status in multiple autoantibodies and the clinical manifestations of RA at an early onset age.

Background Cervical cancer (CC) is the fourth leading cause of death from neoplasms in women and is caused by the human papilloma virus (HPV). Several methods have been developed for the screening of cervical lesions and HPV; however, some socio-cultural factors prevent women from undergoing gynecological inspection, which results in a higher risk of mortality from cervical cancer in certain population groups as indigenous communities. This study aimed to compare the concordance in HPV detection from urine and cervical samples, to propose an alternative to cervical scraping, which is commonly used in the cervical cancer screening. Methodology The DNA from cervical scrapings and urine samples was extracted using the proteinase K method followed by precipitation with alcohol, phenol andchloroform; a modification of the proteinase K method was developed in the management of urine sediment. Viral genotyping was performed using INNOLipa. Results The study population consisted of 108 patients from an indigenous population at southern Mexico, 32 without squamous intraepithelial lesions (NSIL) and 76 with low squamous intraepithelial lesions (LSIL). The majority of NSIL cervical scrapes were negative for HPV (90.63%), whereas more than half of LSIL cases were high-risk HPV positive (51.32%), followed by multiple infection by HR-HPV (17.11%), and multiple infection by LR- and HR-HPV (9.21%). No statistically significant relationship between the cytological diagnosis and the HPV genotypes detected in the urine samples was observed. A concordance of 68.27% for HPV positivity from urine and cervical samples was observed. Similarly, a concordance of 64.52% was observed in the grouping of HPVs by oncogenic risk. HR-HPV was detected in 71% of the urine samples from women with LSIL diagnosis, which suggests that HR-HPV detected in a urine sample could indicate the presence or risk of developing SIL. Conclusion HR-HPV detection in urine samples could be an initial approach for women at risk of developing LSIL and who, for cultural reasons, refuse to undergo a gynecological inspection.

Background: The reemergence of measles represents a public health problem. The aim of the study was to determine the seroprevalence of IgG antibodies against measles in children of three ethnic groups in southern Mexico and the nutritional status and demographic risk factors associated. Methods: A cross-sectional study in 416 school-age children, 207 belonging to the Tlapaneco ethnic group, 101 to the Mixteco group and 108 were considered Mestizo. Sociodemographic data were collected, an anthropometric evaluation of the children was performed and a fasting blood sample was obtained from each child for the measurement of measles IgG antibodies by Enzyme-Linked Immunosorbent Assay (ELISA). Results: From the total sample, 59% of the children were seropositive for IgG antibodies against measles, in contrast, 41% lacked IgG antibodies. Measles antibody seropositivity was higher in girls (64%). 90.5% of 6-year-old children had higher antibodies seroprevalence, compared to the children between 10 and 13 years old (45.5%). In the three ethnic groups, age was negatively correlated with the index standard ratio (ISR) of measles antibody levels and the families with ≥8 members showed less seropositivity. According to the antibodies levels, most of the positive cases remained around 1 Standard Deviation (SD) of the ISR values and no underweight children had antibody levels above 2 SD. Conclusions: The Anti-Measles serological coverage is low in children of three ethnic groups from Southern Mexico and the age, sex, malnutrition and family size are associated factors. Therefore, it is important to strengthen immunization campaigns, principally in vulnerable groups.

Macrophage migration inhibitory factor (MIF) has been associated with the pathogenesis of several rheumatic diseases. In systemic sclerosis (SSc) it has been shown that MIF expression is dysregulated in serum and skin. However, the MIF receptor, CD74, has been poorly investigated and its potential role in the pathogenesis of SSc remains unknown. This study aimed to analyze mRNA, tissue, and serum expression of MIF and CD74 in patients with limited (lcSSc) and diffuse (dcSSc) systemic sclerosis. A case-control study in 20 SSc patients and 20 control subjects (CS) from southern Mexico was conducted. MIF and CD74 mRNA expression levels were quantified by real-time PCR, MIF serum levels were measured by an ELISA kit, and MIF and its receptor CD74 were evaluated by immunohistochemistry of skin biopsies. MIF mRNA expression was significantly higher in CS than in SSc patients (p = 0.02), while CD74 showed no differences between patients and CS. MIF serum levels were similar between SSc patients and CS: dcSSc = 3.82 ng/ml, lcSSc = 3.57 ng/ml, and CS = 3.28 ng/ml. In skin biopsies of SSc, MIF and CD74 were enhanced in keratinocytes, while they showed decreased expression in endothelial cells. On the other hand, the staining of CD74 was high in fibroblasts of dcSSc patients. Our findings show MIF and CD74 deregulation at the transcriptional and translational levels in SSc, which might be associated with the proinflammatory process leading to tissue remodeling and excessive fibrosis in SSc.

Cardiometabolic status is a key factor in mortality by cardiovascular disease (CVD) in systemic lupus erythematosus (SLE). This study evaluated the association of cardiometabolic risk status with clinical activity and damage in SLE patients. A cross-sectional study was conducted in 158 SLE patients and 123 healthy subjects (HS). Anthropometry, glucose, hs-CRP, lipid profile, oxLDL, sCD36, anti-oxLDL antibodies, and cardiometabolic indexes were evaluated. SLE patients had dyslipidemia, higher sCD36, anti-oxLDL antibodies, hs-CRP, and risk (OR 2) to present Castelli score ≥ 4.5, HDL-C 40 mg/dL and LDL-C ≥ 100 mg/dL. Disease evolution time was correlated with glucose and BMI, damage with TG, and clinical activity with TG, TG/HDL-C ratio, and Kannel index. Active SLE patients had risk (OR 2) to present a Castelli score ≥ 4.5, Kannel score ≥ 3, TG/HDL-C ratio ≥ 3 and HDL-C 40 mg/dL. In conclusion, SLE patients have high cardiometabolic risk to CVD related to disease evolution time, and clinical activity.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by elevated levels of pro-inflammatory cytokines, such as interleukin (IL)-6, IL-17, and macrophage migration inhibitory factor (MIF). MIF induces IL-17 secretion and MIF promoter polymorphisms influence the expression of selected downstream mediators. The aim of this study was to investigate the relationship between known functional MIF haplotypes and Th17-related cytokine secretion profile in peripheral blood mononuclear cells (PBMC) from control subjects (CS) and RA patients stimulated with lipopolysaccharide (LPS) and recombinant human MIF (rhMIF). The −794 CATT5-8 and −173G > C polymorphisms of the MIF gene were determined by conventional PCR and PCR-RFLP, respectively. The most frequent haplotypes of the MIF polymorphism and PBMC were identified from three subjects homozygous for each haplotype and in both study groups, the PBMC were obtained and stimulated with LPS or rhMIF. The secretion of cytokines related to the Th17 profile was determined by a multiplex immunoassay (MAGPIX). LPS stimulation induced the secretion of cytokines related to the Th17 profile in PBMC from CS and RA patients, whereas, rhMIF only stimulated this response in PBMC from RA patients. PBMC from CS carriers of the MIF 7C haplotype showed more IL-17A, IL-17F, IL-22, and IL-23 secretion than non-7C carriers after LPS stimulation. In the case of rhMIF stimulation, the PBMC from CS carriers of the 7C haplotype secreted more IL-17A and IL-23 than non-7C carriers. In conclusion, genetic variants of the MIF promoter modulate the secretion of cytokines related to the Th17 profile in PBMC from CS inducing a differential response in comparison to PBMC from RA patients.

Background and objectives The protein tyrosine phosphatase non-receptor type 22 ( PTPN22 ) gene encodes an important negative regulator of T-cell activation, lymphoid-specific phosphatase – Lyp – and has been associated with different autoimmune disorders. The PTPN22 −1123G>C polymorphism appears to affect the transcriptional control of this gene, but to date, the biological significance of this polymorphisms on rheumatoid arthritis (RA) risk remains unknown. We evaluate the association of PTPN22 −1123G>C polymorphism with anti-cyclic citrullinated protein antibodies (anti-CCP) and risk for RA in population from Western Mexico. Materials and methods A transversal analytic study, which enrolled 300 RA patients classified according to ACR-EULAR criteria and 300 control subjects (CS) was conducted. The −1123G>C polymorphism was genotyped by PCR-RFLP. The anti-CCP antibodies levels were quantified by ELISA kit. Results We found a higher prevalence of homozygous PTPN22 −1123CC genotype in CS than in RA patients (OR 0.41; 95% confidence interval 0.24–0.71; p = 0.001), suggesting a potential protective effect against RA. Concerning anti-CCP levels, the CC genotype carriers showed the lowest median levels in RA ( p Conclusion The PTPN22 −1123CC genotype is a protector factor to RA in a Mexican-mestizo population and is associated with low anti-CCP antibodies.

The goals of our study were to determine the possible association of interleukin (IL)-31 with Th17 cytokine profile in serum and to quantify retinoic acid-related orphan receptor C ( RORC) mRNA expression in psoriatic arthritis (PsA) patients. This cross-sectional study was conducted in 50 patients with PsA and 30 control subjects (CS) matched by age and gender. The cytokine serum levels were quantified by magnetic bead–based assay using the Bio-Plex MAGPIX system, and RORC mRNA expression was determined by quantitative polymerase chain reaction (qPCR). As a result, significant differences in IL-31 were observed between study groups (77.23 pg/mL in PsA vs 64.4 pg/mL in CS, P s = 0.64, P s = 0.73, P s = 0.70, P s = 0.54, P = 0.002; IL-23: rs = 0.5, P

Background Macrophage migration inhibitory factor (MIF) is a cytokine capable of stimulating inflammatory cytokine and matrix metalloproteinase production from macrophages and synovial fibroblasts, which leads to persistent inflammation and bone degradation, two of the major pathological processes in rheumatoid arthritis (RA). The aim of this study was to evaluate the association of MIF promoter polymorphisms (−794CATT5‐8 rs5844572 and −173G > C, rs755622), circulating MIF levels, and mRNA expression with RA susceptibility and disease activity. Methods A case–control study was conducted in 200 RA patients and 200 control subjects (CS) from Southern Mexico. Genotyping was performed by conventional PCR and PCR‐RFLP methods. MIF mRNA expression was quantified by real‐time PCR and MIF serum levels were determined by an ELISA kit. Results The 7,7 (−794CATT5‐8) and −173CC (−173G > C) genotypes were associated with higher disease activity in RA patients. MIF serum levels were increased, and MIF mRNA expression was reduced in RA patients as compared to CS. In addition, RA patients with moderate disease activity had higher MIF levels than those with low disease activity. The −794CATT5‐8 and −173G > C MIF polymorphisms were not associated with RA susceptibility. Conclusion These results suggest an important role of MIF polymorphisms and MIF serum levels with disease activity in RA., MIF −794CATT5‐8 and −173G > C polymorphisms are not associated with RA susceptibility risk in a southern Mexican population. The 7,7 (−794CATT5‐8) and GC (−173G > C) genotypes are associated with high‐ and low disease activity, respectively. Higher MIF serum levels are associated with moderate disease activity in RA patients.

Paraoxonase 1 (PON1) promotes antioxidant and antiatherogenic activity related to the hydrolysis of oxidized lipids of low-density lipoproteins. In rheumatoid arthritis (RA) patients, it has been reported that low PON1 activity is related to an impaired lipid profile, increasing cardiovascular risk (CVR). The goal of this study was to analyze the effect of common PON1 polymorphisms and haplotypes on enzymatic activity, PON1 serum levels (PON1s), and lipid parameters related to atherogenic profile in RA patients.A cross-sectional study was carried out on 250 Mexican patients with RA. The lipid profile was determined by colorimetric tests. The PON1 activity (CMPAase) was measured by spectrophotometry. The levels of PON1s were determined by ELISA, and the polymorphisms in the PON-1 gene (-108CT, L55M, and Q192R) were genotyped by the PCR-RFLP method. The haplotypes were estimated and statistical analysis was performed.The median of the CMPAase activity and PON1 levels was 13.91 U/mL and 24.75 ng/mL, respectively. The CMPAase activity was significantly lower in carriers of -108TT and 192QQ genotypes (β = - 4.09, P = 0.001 and β = - 3.73, P = 0.002, respectively); moreover, the PON1 levels were lower in 192Q allele carriers (P 0.01). The TLQ haplotype was associated with CMPAase activity 13.91 U/mL (OR = 2.29, P 0.001), as well as with levels of PON1s 24.75 ng/mL (OR = 1.65, P = 0.017). In this study, the CMPAase activity ( 13.91 U/mL) showed a positive association with lower levels of high-density lipoprotein cholesterol (HDL-c; 40/50 mg/dL), and with a triglycerides/HDL-c ratio 3%, and a total cholesterol/HDL-c ratio 4.5/5%, all representatives of an atherogenic risk lipid profile.PON1 polymorphisms modulate the CMPAase activity and PON1 levels in Mexican patients with RA. The CMPAase activity 13.91 U/mL is associated with an atherogenic lipid profile, independently of inflammation markers and treatment with anti-rheumatic drugs. Key Points •The haplotype TLQ is a marker for low PONase activity in rheumatoid arthritis. •The haplotype TLQ is a marker for low PON1 serum levels in rheumatoid arthritis. •The enzymatic PON1 activity represents the best marker for an atherogenic lipid profile in rheumatoid arthritis, in comparison with PON1 levels. •The haplotype TLQ is a marker of low PON1 activity, levels of PON1s, and atherogenic lipid profile, independent of treatment therapy in rheumatoid arthritis.

Obesity and nutrients intake deficiencies may contribute to the clinical manifestations and inflammatory processes in systemic lupus erythematosus (SLE). The aim of this study was to assess the relationship between nutritional status and dietary intake with clinical variables in Mexican-mestizo SLE patients. A cross-sectional study was conducted in 130 female SLE patients, classified by the 1997 SLE American College of Rheumatology (ACR) criteria, the clinical activity was evaluated by the Mexican-Systemic Lupus Erythematosus-Disease Activity Index (Mex-SLEDAI), body mass index (BMI) by the World Health Organization (WHO) criteria, the energy calculation and nutritional intake were performed by Nutritionist Pro Diet software. SLE patients with excess weight (BMI &gt, 25 kg/m2) showed a higher score of clinical activity (Mex-SLEDAI = 2, p = 0.003), higher clinical activity prevalence (40.9%, p = 0.039) and a significant association for high clinical activity (odds ratio (OR) = 2.52, 95% confidence interval (CI) = 1.08&ndash, 5.9, p = 0.033), in comparison with patients without excess weight (BMI &lt, 25 kg/m2). In particular, the excess weight increased the Mex-SLEDAI score (&beta, coefficient = 1.82, R2 = 0.05, p = 0.005). Also, the SLE patients presented a high prevalence (%) of deficient consumption (cut-off point: &lt, 67% of dietary adequacy) of vitamin E (100%), iodine (96%), omega 3 (93.44%), biotin (78%), vitamin K (73.33%), iron (67%), vitamin D (63.3%), potassium (59%), folic acid (56.67%), pantothenic acid (43.3%), vitamin A (41.67%) and zinc (32%). In conclusion, in SLE patients the excess weight was associated with increased clinical activity and to the presence of deficiencies in some essential nutrients ingested.

Background The use of antirheumatic drugs is key to limit or prevent inflammation and joint damage in rheumatoid arthritis (RA). Recently, neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) has been considered markers of clinical activity in RA1, however its relationship with serological and clinical parameters in patients receiving disease modifying drugs (DMARDs) therapy has been poorly evaluated. Objectives To analyze the association of NLR and PLR with serological and clinical parameters related to the clinical prognosis in RA patients with antirheumatic treatment. Methods A cross-sectional study was carried out in 150 women with RA (mean age of 45.5 years, and mean duration of disease of 8 years) all diagnosed according to ACR/EULAR 2010 criteria and receiving DMARDs and corticosteroids (Cs) therapy. The clinical features and DAS-28 score were analyzed by a rheumatologist professional. The NLR and PLR, as well as the erythrocyte sedimentation rate (ESR), high sensitivity C reactive protein (hsCRP) levels, rheumatoid factor (RF) and anti-cyclic citrullinated peptides (anti-CCPs) antibodies, were determined in the laboratory. Results The medical schemes prescribed commonly were: Methotrexate (MTX) monotherapy and MTX combination with chloroquine, sulfasalazine, leflunomide and Cs. The NLR was correlated with DAS28-ESR and DAS28-hsCRP scores. The values of NLR >2.2 (percent neutrophil/percent lymphocyte) were associated with hsCRP >12 mg/L (OR=2.45, p=0.036), DAS28-hsCRP >5.1 (OR=2.69, p=0.07) and with anti-CCPs-positive (>5 U/mL) (OR=1.57, p=0.41). While, PLR >10.4 (platelet count×103/mm3/percent lymphocyte) was too associated (OR=3.72, p=0.004; OR=2.51, p=0.08; OR=2.96, p=0.07, respectively). Serological autoantibodies, when was considered in combination, the anti-CCPs/RF-positive patients showed a higher correlation between NLR and PLR with the parameters of clinical activity [tender joints count (r=0.19, p=0.036; r=0.16, p=0.07), swollen joints count (r=0.15, p=0.08; r=0.14, p=0.11) and DAS28-hsCRP score (r=0.16, p=0.06; r=0.17, p=0.05)], however this correlation was higher in anti-CCPs-positive but RF-negative patients. In addition, was observed that patients with DMARDs combination and a greater number of drugs had increased NLR and PLR. Conclusion NLR and PLR could be considered markers for the evaluation of the clinical course and response to therapy DMARDs in RA patients. Reference [1] Sargin G, Senturk T, Yavasoglu I, et al. Relationship between neutrophil-lymphocyte, platelet-lymphocyte ratio and disease activity in rheumatoid arthritis treated with rituximab. Int J Rheum Dis. 2018. doi.org/10.1111/1756-185X.13400 Disclosure of Interests None declared

Background: Sarcopenia play an important role in the quality of life, morbidity and mortality of the patients, especially in who suffer chronic disease. In rheumatoid arthritis (RA) sarcopenia risk is higher due to joint dysfunction, pharmacological therapy and chronic inflammation1; these conditions may induce changes in body composition such as an increase in visceral fat associated to reduced muscle mass. Recently emerge the concept of sarcopenic obesity, however the association to clinic characteristics and pharmacotherapy in RA has not been established. Objectives: We investigated the prevalence of sarcopenia and sarcopenic obesity, as well as the relationship with glucocorticoids (GCs) use and clinic characteristic of RA patients from southern Mexico. Methods: We carried out a cross-sectional study in 223 RA patients (89% women, mean age 44 years), all diagnosed according to ACR/EULAR 2010 criteria. The body composition was examined using a bioimpedance method (body weight, muscle mass, body fat, etc.). Abdominal obesity was defined by WHO criteria and the hand grip strength was evaluated by dynamometry. Sarcopenia was defined according to The European Working Group on Sarcopenia in Older People, as Skeletal Muscle Mass Index less than 5.45 kg/m2 in women and less than 7.26 kg/m2 in men, while sarcopenic obesity was defined by the presence of sarcopenia more abdominal obesity. The GCs use and dosage (prednisone and methylprednisolone) were analyzed reviewing the clinical records. Anti-cyclic citrullinated peptides (anti-CCP) antibodies, rheumatoid factor (RF) levels, high sensitivity C reactive protein (hsCRP), erythrocyte sedimentation rate (ESR) were determinate. The morning stiffness, clinic activity of disease (DAS28-ESR score) and disability index functional (HAQ-DI) were measurement. Results: In this study 86% of the population had sarcopenia and 44% sarcopenic obesity. The 62.8% under GCs therapy. The prednisone dosage was positively associated to sarcopenia (>5 mg/day; OR=4.3, p=0.003) and sarcopenic obesity (OR=3.2, p=0.06). The intramuscular pulse of methylprednisolone (40 mg/kg) was associated to sarcopenic obesity phenotype (OR=2.61, p=0.09). Regarding the clinical and serological markers in RA, high disease activity (DAS28-ESR score) was associated to sarcopenia (OR=6.6, p=0.01) and sarcopenic obesity (OR=6.3, p=0.02). The morning stiffness (p=0.03), RF (p=0.05), anti-CCP positive (p=0.03) and HAQ-DI score (p=0.04) were too associated, mainly to sarcopenic obesity. Conclusion: Sarcopenia and sarcopenic obesity are associated to GCs dosage and with serological and disease activity markers in RA patients from southern Mexico. So that is needed promote monitoring and management of sarcopenia and sarcopenic obesity in RA patients. Reference: [1] Torii M, Hashimoto M, Hanai A, et al. Prevalence and factors associated with sarcopenia in patients with rheumatoid arthritis. Mod Rheumatol. 2018;1-7. doi: 10.1080/14397595.2018.1510565 Disclosure of Interests: None declared

Background: The risk of cardiovascular disease in rheumatoid arthritis (RA) patients is 1.5 times higher compared to the general population. Some factors relationships to cardiovascular disease in RA are high clinic activity of the disease, the autoantibodies-positive, the disease duration and pharmacological treatment1, as well as single nucleotide polymorphisms. Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate metabolism and is considered a drug-metabolizing enzyme; MTHFR 677C/T polymorphism was described leading to reduced enzyme activity, increasing serum concentration of homocysteine, an intermediate product of methotrexate metabolism. Paraoxonase 1 (PON1) is a multifunctional enzyme that can detoxify through its homocysteine thiolactonase activity, the polymorphism identified in the position PON1 -108C/T exerts effects on serum activity and expression levels. Objectives: We evaluate the association between the interaction MTHFR 677C/T and PON1 -108C/T polymorphisms and cardiovascular risk (CVR) in RA patients. Methods: A cross-sectional study was performed including 250 RA patients diagnosed according to ACR/EULAR 2010 criteria, attended in a public hospital from southern Mexico. MTHFR 677C/T and PON1 -108C/T genotypes were determined by PCR-RFLP method. The clinic and metabolic parameters were evaluated. CVR was defined using different diagnostic tools. Logistic regression models were used to evaluate the association between interaction polymorphisms and CVR. Results: We show high CVR in a variable prevalence according to diagnostics tools: TGs/HDL-c (64.8%), Castelli (50%) and Kannel (43%). Alleles frequency of 667C/T were 33% for C and 67% for T allele; PON1-108C/T 52% for C and 43% for T allele. In a multiple regression model adjusting by duration of disease, pharmacological therapy and DAS28-hsCRP score, carriers of the 667TT and -108CC genotypes had higher CVR according to TGs/HDL-c (>3%) (OR=4.68, p=0.019), Castelli (>3%) (OR=2.99, p=0.03) and Kannel index (>4.5% in woman and >5% in men) (OR=2.03, p=0.13). Conclusion: Our results demonstrate an interaction between MTHFR 677C/T and PON1 -108C/T polymorphisms on the CVR, associated to atherogenic indexes in RA patients from southern Mexico. References [1] Mackey RH, Kuller LH, Moreland LW. Cardiovascular disease risk in patients with rheumatic diseases. Clin Geriatr Med. 2017;33(1):105-117. doi: 10.1016/j.cger.2016.08.008. Disclosure of Interests: None declared

Background: The aim of the present study was to determine the association between the health-related quality of life (HRQoL) with sociodemographic parameters and lifestyle during COVID-19 confinement in Mexico, Chile, and Spain. Methods: A cross-sectional pilot study, with 742 observations of online surveys in 422, 190, and 130 individuals from Mexico, Chile, and Spain, respectively. Sociodemographic data, presence of comorbidities, food habits, and physical activity (PA) patterns were evaluated. The HRQoL was evaluated according to the SF-36 Health Survey. The multilinear regression analysis was developed to determine the association of variables with HRQoL and its physical and mental health dimensions. Results: The female sex in the three countries reported negative association with HRQoL (Mexico: β −4.45, p = 0.004; Chile: β −8.48, p < 0.001; Spain: β −6.22, p = 0.009). Similarly, bad eating habits were associated negatively with HRQoL (Mexico: β −6.64, p < 0.001; Chile: β −6.66, p = 0.005; Spain: β −5.8, p = 0.032). In Mexico, PA limitations presented a negative association with HRQoL (β −4.71, p = 0.011). In Chile, a sedentary lifestyle (h/day) was linked negatively with HRQoL (β −0.64, p = 0.005). In Spain, the highest associations with HRQoL were the presence of comorbidity (β −11.03, p < 0.001) and smoking (β −6.72, p = 0.02). Moreover, the PA limitation in Mexico (β −5.67, p = 0.023) and Chile (β −9.26, p = 0.035) was linked negatively with mental health. Conclusions: The bad eating habits, PA limitations, female sex, comorbidity presence, and smoking were parameters linked negatively with HRQoL.

Introduction : Prolactin (PRL) is a 23-kDa protein that can be synthesized and secreted by pituitary and extrapituitary tissues such as immune cells due to its expression being regulated by two independent promoter regions. The promoter which is responsible for extrapituitary expression contains the single nucleotide polymorphism (SNP) –1149 G/T previously associated with autoimmune diseases in various populations. This study evaluates the relationship of PRL –1149 G/T polymorphism with PRL serum levels and clinical characteristics in systemic lupus erythematosus (SLE) patients from western Mexico. Material and methods: One hundred and sixty-three SLE patients classified according to the 1982 American College of Rheumatology (ACR) SLE classification criteria and 326 unrelated control subjects (CS), both from western Mexico, were included. The PRL –1149 G/T polymorphism was genotyped using the polymorphism was performed by the polymerase chain reaction restriction fragment length polymorphism technique, and both PRL serum levels and autoantibodies were measured by enzyme-linked immunosorbent assay (ELISA). Results : We found an association between the PRL –1149 TT genotype and SLE according to the recessive genetic model (OR = 2.26, 95% CI: 1.01–5.08, p = 0.04). The TT genotype was associated with anti-RNP antibodies (p = 0.04) and with higher scores of the Mex-SLEDAI (p = 0.02). Moreover, SLE patients showed elevated PRL serum levels (12.4 ng/ml; p < 0.01), and this condition was associated with renal activity and the presence of anti-RNP antibodies. Conclusions : PRL –1149 TT genotype is associated with susceptibility to SLE in a Mexican-Mestizo population, and high PRL serum levels are associated with anti-RNP antibodies and renal activity.

Objective Few studies have investigated the relationships between high-sensitivity C-reactive protein (hs-CRP) concentration and conventional cardiometabolic markers in young adults. The aim of this study was to characterize the cardiometabolic profile of young adults who are at high cardiovascular risk, according to hs-CRP concentration. Methods A cross-sectional study was conducted in 300 young adults (18 to 30 years old) from southern Mexico (n = 150 normal-weight and n = 150 obese). Their circulating lipid and glucose concentrations were measured using colorimetric enzymatic assays, and their hs-CRP, ApoA, and ApoB concentrations were measured using turbidimetric assays. Results The most prevalent abnormalities in the participants with high cardiovascular risk, determined using an hs-CRP >28.57 nmol/L, were high waist circumference (85.7%), obesity (83.9%), high low-density lipoprotein-cholesterol (64.3%), low high-density lipoprotein-cholesterol (50%), Apo B in the highest tertile (39.3%), hypertriglyceridemia (35.7%), and high blood pressure (30.4%). In addition, there were strong associations between hs-CRP >28.57 nmol/L and obesity (odds ratio [OR] = 13.9), high waist circumference (OR = 8.0), hypertriglyceridemia (OR = 4.0), high blood pressure (OR = 3.4), hypercholesterolemia (OR = 2.8), and Apo B in the highest tertile (OR = 2.4). Conclusion The principal cardiometabolic alterations associated with high cardiovascular risk, determined using hs-CRP, are obesity, dyslipidemia, and high blood pressure in young adults.

Prolactin (PRL) is a sex hormone with immunomodulatory properties, and it is associated with the clinical activity of rheumatoid arthritis (RA). The -1149G>T polymorphism at the prolactin (PRL) gene has been associated with autoimmune diseases, but its functional effect is unclear. To analyze the association of the PRL -1149G>T polymorphism with disease susceptibility, mRNA, and protein expression of PRL in RA patients from Southern Mexico. We included 300 RA patients and 300 control subjects (CS). Genotypes were identified by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique, the PRL mRNA expression was determined by real-time PCR, and PRL serum levels were measured by enzyme-linked immunosorbent assay. Applying genetic models of inheritance (dominant, recessive, and additive), we found an association between the T allele and decreased RA susceptibility (OR = 0.55, 95% CI 0.35–0.87, p = 0.009; OR = 0.09, 95% CI 0.012–0.76, p = 0.011; OR = 0.49, 95% CI 0.32–0.76, p = 0.001, respectively). RA patients had higher mRNA expression and soluble levels of PRL than CS (p

Type 2 diabetes is a disease with a high global prevalence, characterized by chronic hyperglycemia, insulin resistance, polyphagia, polydipsia, polyuria, and changes in body weight. Animal models have been very useful for the study of this disease and to search for new therapeutic targets that delay, attenuate, or avoid diabetic complications. The purpose of this work was to establish a model of type 2 diabetes and exhibit the majority of the characteristics of the disease. Two-day-old male and female Wistar rats were treated once with streptozotocin (70 or 90 mg/kg body weight). After weaning, they were given a sucrose-sweetened beverage (SSB; sucrose at 10 or 30%) during 7 or 11 weeks; their body weight and food intake were measured daily. With the rats at 14 weeks of age, we determined the following: (a) fasting blood glucose, (b) oral glucose tolerance, and (c) insulin tolerance. We found that the supplementation of sucrose at 10% for 7 weeks in male rats which had previously been given streptozotocin (70 mg/kg) at neonatal stage leads to the appearance of the signs and symptoms of the characteristic of type 2 diabetes in adulthood.

Background /Aim: The hypertriglyceridaemic waist (HTGW) phenotype has been described and suggested in general population as a cardiovascular risk marker. The aim of the present study was to evaluate the HTGW phenotype as a marker related to HUC and MetS in rheumatoid arthritis (RA). Materials and methods This was a cross-sectional study was designed in 250 RA Mexicans patients. The HTGW phenotype was defined as elevated waist circumference and elevated triglyceride concentration. Logistic regression analysis was used to evaluate the association between the HTGW phenotype, HUC and MetS in its traditional NCEP/ATPIII versions and modified (HTGWm and MetSm). Results The prevalence of HTGW and HTGWm it was 20.4% and 32%, respectively. All patients with HTGW presented MetS ( P 0.001), and in a multivariate model, the HTGW phenotype was the marker most closely related to HUC in comparison to components of MetS. Conclusion The HTGW may represent a marker for screening of cardiometabolic risk in RA patients, so in clinical practice can be implemented as a low-cost marker in the evaluation of the patient regardless of clinical characteristics of disease.

Systemic sclerosis (SSc) is a complex autoimmune disease, characterized by microvascular lesions, autoimmunity, and fibrosis. It is suggested that MIF participates in the amplification of the proinflammatory process in SSc; moreover, the promoter polymorphisms − 794 CATT5–8 (rs5844572) and − 173G>C (rs755622) in the MIF gene have been associated with an increase in MIF serum levels in several autoimmune diseases. The aim of this study was to analyze the relationship of the − 794 CATT5–8 and − 173G>C MIF polymorphisms with mRNA expression, MIF serum levels, and the Th1/Th2/Th17 cytokine profile in SSc. A case-control study was carried out that included 50 patients with SSc and 100 control subjects (CS). Both polymorphisms were genotyped by PCR and PCR-RFLP. MIF levels were measured by ELISA kit. The cytokine profile and the MIF mRNA expression were quantified by BioPlex MagPix system and real-time PCR, respectively. An association between the − 794 CATT7 and − 173*C MIF alleles and the 7C haplotype with SSc susceptibility was found (p

BACKGROUND: CD40 is a costimulatory molecule for B cells, and CD154 is a marker of CD4+ T cells activation. CD40‐CD154 interaction promotes pro‐inflammatory cytokines secretion and autoantibodies production. PTPN22 gene encodes LYP protein, an inhibitor of T‐ and B‐cell activation. PTPN22 1858C>T polymorphism confers rheumatoid arthritis (RA) susceptibility. Hence, we evaluate the relationship between 1858C>T polymorphism with CD40 and CD154 expression and IFN‐γ secretion in RA patients. METHODS: PTPN22 1858C>T polymorphism was genotyped in 315 RA patients and 315 control subjects (CS) using PCR‐RFLP method. Later, we selected only ten anti‐CCP‐positive RA patients, naïve to disease‐modifying antirheumatic drugs and ten CS, all with known 1858C>T PTPN22 genotype. The CD40 and CD154 membrane expressions were determined by flow cytometry in peripheral B and T cells, correspondingly. RESULTS: The B cells percentage and mCD40 expression were similar between RA and CS (P > 0.05) and we did not find an association between these variables and the 1858C>T polymorphism. The CD4+ T cells percentage was higher in RA patients than CS (P = 0.003), and in the RA group, the CD4+ T cells percentage and mCD154 expression were higher in the 1858 T allele carriers (P = 0.008 and P = 0.032, respectively). The IFN‐γ levels were lower in RA patients carrying the PTPN22 risk allele (P = 0.032). CONCLUSION: The PTPN22 1858 T risk allele is associated with increased CD4+ T cells percentage and high mCD154 expression in RA patients, which could favor the pro‐inflammatory cytokine release and the establishment of the inflammatory response at the seropositive RA.

Background The hand is an anatomical structure with a large number of joints; its prehensile grasp capability constitutes a highly specialised biomechanical function. In rheumatoid arthritis (RA), the structures of the joint are damaged by the characteristic inflammatory process 1 The Disease Activity Score (DAS28) considers twenty hand joints in the evaluation of rheumatoid arthritis (RA). While the Health Assessment Questionnaire (HAQ) disability index (DI) (HAQ-DI) is the most frequently used instrument for measuring self-reported physical function in rheumatoid arthritis and considers the ability to dress and groom, get up, eat, hygiene, reach, grasp, situations in which the functional capability of the hand is crucial. Objectives To assess the relationship between hand prehensile strength, the DAS28 index and HAQ-DI score in patients with diagnosis of RA. Methods The prehensile strength was obtained by the dynamometry method from 105 AR patients, the maximum strength levels in the dominant and non-dominant hand were considered. The Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR) and HAQ-DI were recorded. Results The maximum prehensile strength, on average, was 14 kg, and the weak force category was more prevalent. The prehensile strength of both hands was negatively correlated with the HAQ-DI score and DAS28 index. In an adjusted logistic regression model, the ”weak” strength category of the non-dominant hand was associated with “moderate clinical activity” in the DAS28 score (OR=8.59, p=0.02), while the category of ”weak” strength of the dominant hand was associated with the presence of ”some difficulty” of HAQ-DI score (OR=4.75, p=0.10). Conclusions The decrease in prehensile strength represents a marker associated with the DAS28 index and HAQ-DI score in the patient with RA, regardless of age, muscle mass, total fat or body mass. The measurement of the prehensile strength can be a useful and inexpensive tool to be considered in the clinical evaluation of the RA. Reference [1] Janet L Poole. Hand Function in Rheumatoid Arthritis. Mehmet Tuncay Duruoz A Practical Guide to Assessment. Springer. 2014. [ISBN:978–1–4614–9448–5] Acknowledgements None. Disclosure of Interest None declared

Background Paraoxonase-1 (PON-1) is a high-density lipoprotein (HDL)-associated antioxidant enzyme with anti-atherogenic properties. Although genetic polymorphisms are known to modulate PON-1 activity,1 other factors as the consumption of disease-modifying anti-rheumatic drugs (DMARDs) and nonsteroidal anti-inflammatory drugs (NSAIDs) can also modulate its function.2 Objectives To analyse the association between PON-1 activity according to L55M polymorphism and anti-rheumatic treatment in patients with rheumatoid arthritis (RA) from southern Mexico. Methods Serum PON1 activity, using 4-chlorometyl phenylacetate (4-CMPA) as substrate3 was quantified in 246 RA patients (181 treated with DMARDs, NSAIDs and/or corticosteroids, and 65 without treatment). The PON1 rs854560 genotype (L55M) was determined by the PCR-RFLP method. Results PON-1 activity was decreased in RA patients under treatment anti-rheumatic. In addition, an effect of LM/MM genotype of L55M polymorphism was noted in treated patients who exhibiting the lowest PON-1 activity (10.45 vs 13.91 U/mL, p=0.05). The distribution of L55M genotypes were; 86.8% (LL), 12.8% (LM) and 0.4% (MM). The Leflunamide and diclofenac drugs were associated with the mainly decrease of the PON-1 activity (p Conclusions PON-1 activity is impaired in association with the anti-rheumatic treatment and L55M polymorphism, so in patients with RA the susceptible background genetic could contribute to increasing the cardiovascular risk linked to PON-1 activity. References [1] Leviev I, Deakin S, James RW. Decreased stability of the M54 isoform of paraoxonase as a contributory factors to variations in human serum paraoxonase concentrations. J Lipid Res. 2001;42:528–535. [2] Dilek E, Polat MF. In vitro inhibition of three different drugs used in rheumatoid arthritis treatment on human serum paraoxanase 1 enzyme activity. Protein Pept Lett. 2016;23(1):3–8. [3] Richter RJ, Jarvik GP, Furlong CE. Determination of paraoxonase 1 status without the use of toxic organophosphate substrates. Cir Cardiovasc Genet. 2008;1:147–152. Disclosure of Interest None declared

Background The risk of cardiovascular disease (CVD) is increased in rheumatoid arthritis (RA); about 50% of associated deaths in rheumatoid arthritis (RA) are attributed to CVD.1 Both traditional cardiovascular risk (CVR) factors and inflammation contribute to this risk. The hyperuricemia (HUC) and metabolic syndrome (MetS) are considered parameters of CVR, both closely related,2 and recently the hypertriglyceridemic-waist (HTGW) phenotype has been defined as well a marker to identify HUC in the general population.3 Objectives To determine the prevalence of HTGW phenotype and to evaluate its association with CVR parameters among RA patients. Methods HTGW phenotype was defined as waist girth ≥102 cm in male and ≥88 cm in female and TG >150 mg/dl in 250 patients diagnosed with RA according to the ACR/EULAR 2010 criteria. The levels of uric acid >5.5 mg/dL defined HUC. The MetS and its individual components (NCEP-ATPIII) were evaluated as parameters of CV risk. Results We identified 51 AR patients (20.4%) whith HTGW phenotype. Adjusting for covariates in a logistic regression model, it was observed that the HTGW phenotype is associated with the presence of HUC (OR=6.14, p≤0.001), and MetS (OR=5.7, IC95%, 2.7–12.2, p≤0.001). Conclusions HTGW is prevalent in RA patients from southern Mexico. The HTGW phenotype can be considered at low cost marker, used as a tool screening to predict high metabolic risk during the clinical course of the rheumatic disease. References [1] Goshayeshi L, Saber HR, Sahebari M, et al. Association between metabolic syndrome, BMI, and serum vitamin D concentrations in rheumatoid arthritis. Clin Rheumatol2012;31:1–7. [2] Abbasian M, Ebrahimi H, Delvarianzadeh M, et al. Association between serum uric acid (SUA) levels and metabolic syndrome (MetS) components in personnel of Shahroud university of medical sciences. Diabetes Metab Syndr2016;10:132–6. [3] Chen S, Guo X, Dong S, et al. Association between the hypertiglyceridemic waist phenotype and hyperuricemia: a cross-sectional study. Clin Rheumatol2017;36(5):1111–1119. Acknowledgements None. Disclosure of Interest None declared

Background: The gut microbiota plays an important role in human metabolism; previous studies suggest that the imbalance can cause a metabolic endotoxemia that may be linked to weight gain and insulin resistance. The purpose of this study was to investigate the relationship between the gut microbiota composition, the lipopolysaccharide levels and the metabolic profile in obese and normal-weight young subjects. Methods: We studied 32 obese (BMI ≥ 30 kg/m2) and 32 normal-weight subjects (BMI = 18.5-24.9 kg/m2), aged 18-25 years. Quantification of intestinal bacteria was performed by real-time PCR. Endotoxin units were determined with the test QCL-1000, and biochemical profile was performed under a standard protocol of Spinreact. Results: Obese individuals had a BMI of 34.5 (32.9-36.45) kg/m2, increased triglycerides (123 vs. 70 mg/dl), total cholesterol (168 vs. 142 mg/dl), and LDL-cholesterol (114 vs. 96.5 mg/dl). In obese subjects body temperature was higher than in normal-weight subjects. We found a greater number of Clostridum leptum and Lactobacillus (p < 0.001) and lower numbers of Prevotella and Escherichia coli (p < 0.001) in the obese group. A decrease of E. coli was associated with an increased risk of lipopolysaccharide levels ranging from 1 to 1.3 EU/ml. A positive correlation was found between serum lipopolysaccharides and BMI (r = 0.46, p = 0.008), triglyceride levels (r = 0.44, p = 0.011) as well as waist circumference (r = 0.34, p = 0.040), being more evident in young obese females. Conclusion: Subclinical metabolic endotoxemia determined by serum concentration of lipopolysaccharides was related to the smallest amount of E. coli, high triglyceride levels, and central adiposity in obese young persons.

Summary Antibodies against cyclic citrullinated peptides (anti-CCP) are widely used for diagnosis of rheumatoid arthritis (RA). We performed a comparative analysis of antibodies targeting the citrullinating enzyme peptidylarginine deiminase type 4 (anti-PAD4) and mutated citrullinated vimentin (anti-MCV) with anti-CCP autoantibodies in RA patients and examined their relationships with clinical parameters, cytokine profiles and the PADI4 gene. Autoantibodies were examined by enzyme-linked immunosorbent assay (ELISA) in sera of 170 RA patients and 103 controls. Cytokine profiles were measured using a multiplex system. PADI4 polymorphisms (89G > A, 90T > C and 92G > C) were genotyped by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). Anti-PAD4, anti-MCV and anti-CCP autoantibodies were detected in 24, 61 and 74% of RA patients, respectively. Positive correlations were observed between anti-PAD4 and disease duration; anti-CCP and erythrocyte sedimentation rate (ESR); anti-MCV and ESR and C-reactive protein. Anti-MCV antibodies were associated with high disease activity score 28 (DAS-28) in early RA. Concentrations of T helper type 1 (Th1) [tumour necrosis factor (TNF)-α, interleukin (IL)-12, IL-2, IL-1β], Th2 (IL-4, IL-6, IL-10, IL-13) and Th17 (IL-17) cytokines were higher in RA than in controls. Th2 and, to a lesser extent, Th1-related cytokines, showed positive correlations with anti-MCV and anti-CCP. The GTG haplotype in PADI4 was associated with anti-CCP and anti-MCV, but not anti-PAD4 antibodies. In conclusion, anti-PAD4 antibodies are detected mainly in established RA, which is in contrast to the early detection of antibodies against citrullinated peptide/proteins (ACPAs). Among autoantibodies, anti-MCV appear to perform better as markers of disease activity. Furthermore, anti-CCP and anti-MCV are associated genetically with the citrullinating enzyme PAD4 and are related strongly to Th1 and Th2 cytokines, suggesting a feed-forward loop between cytokines and ACPA production.

Objective: To assess whether the -675 4G/5G polymorphism in the plasminogen activator inhibitor-1 gene is associated with obesity and insulin resistance in Mexican children. Methods: A cross-sectional study was performed in 174 children, 89 with normal-weight and 85 with obesity, aged from 6 to 13 years. All children were from state of Guerrero, and recruited from three primary schools in the city of Chilpancingo, state of Guerrero, Mexico. Insulin levels were determined by immunoenzymatic assay. The homeostasis model assessment was used to determine insulin resistance. The -675 4G/5G polymorphism in PAI-1 gene was analyzed by polymerase chain reaction-restriction fragment length polymorphism. Results: The prevalence of insulin resistance in the obese group was higher (49.41%) than in the normal-weight group (16.85%). The 4G/5G PAI-1 polymorphism was found in Hardy Weinberg equilibrium. The 4G/5G genotype contributed to a significant increase in waist-hip ratio (β = 0.02, p = 0.006), waist circumference (β = 4.42, p = 0.009), and subscapular skinfold thickness (β = 1.79, p = 0.04); however, it was not related with insulin resistance. Conclusion: The -675 4G/5G genotype of PAI-1 gene was associated with increase of body adiposity in Mexican children. Resumo: Objetivo: Elaboramos este estudo para avaliar se o polimorfismo -675 4G/5G no gene inibidor 1 do ativador do plasminogênio se associa à obesidade e à resistência insulínica em crianças mexicanas. Métodos: Foi realizado um estudo transversal em 174 crianças, 89 delas com peso normal e 85 obesas, variando sua idade de 6 a 13 anos. Todas as crianças eram do estado de Guerrero e foram recrutadas de três escolas primárias na cidade de Chilpancingo, México. Os níveis de insulina foram determinados por prova imunoenzimática. Foi usado o modelo de avaliação da homeostase para determinar resistência insulínica. O polimorfismo -675 4G/5G no gene PAI-1 foi analisado pelo método reação de polimerase em cadeia-polimorfismo no comprimento dos fragmentos de restrição. Resultados: A prevalência de resistência insulínica no grupo obeso foi mais alta (49,41%) do que no grupo com peso normal (16,85%). O polimorfismo 4G/5G do PAI-1 foi encontrado em equilíbrio de Hardy Weinberg. O genótipo 4G/5G contribuiu para um aumento significativo da relação cintura-quadril (β = 0,02, p = 0,006), da circunferência da cintura (β = 4,42, p = 0,009) e da espessura da prega subescapular (β = 1,79, p = 0,04), mas não se relacionou com a resistência insulínica. Conclusão: O genótipo -675 4G/5G do gene PAI-1 se associou a aumento da adiposidade corporal em crianças mexicanas. Keywords: PAI-1 gene, Polymorphisms, Body adiposity, Insulin resistance, Palavras-chave: Gene PAI-1, Polimorfismos, Adiposidade corporal, Resistência insulínica

Several single nucleotide polymorphisms (SNPs) within the CTLA-4 gene and elevated serum levels of soluble CTLA-4 (sCTLA-4) have been associated with autoimmunity including rheumatoid arthritis (RA). In this case–control study, we evaluated the relationship between the −319C/T (rs5742909) and CT60 G/A (rs3087243) SNPs and sCTLA-4 levels in 200 RA patients and 200 control subjects (CS) from Western Mexico. Both SNPs were genotyped with the polymerase chain reaction–restriction fragment length polymorphism technique and the sCTLA-4 levels were quantified using an enzyme-linked immunosorbent assay kit. In addition, we performed a haplotype analysis, including our previous data of the +49A/G (rs231775) SNP. The G/A genotype of the rs3087243 SNP was associated with a decreased risk of RA [odd ratio (OR) 0.61, 95 % confidence interval (CI) 0.38–0.96, p = 0.024]. This protection was also observed in the negative anti-cyclic citrullinated peptide group of RA carriers of the A allele (OR 0.48, 95 % CI 0.22–1.05, p = 0.042). On the contrary, we identified the −319C/+49G/CT60G haplotype of CTLA-4 gene as a risk factor for RA (OR 1.69, 95 % CI 1.13–2.52, p = 0.01). The sCTLA-4 levels were not associated with RA (p = 0.377), but were correlated with the functional disability of these patients (r = 0.282, p = 0.012). However, in CS the C/T genotype of the rs5742909 SNP, as well as the G/G and G/A genotypes of the rs3087243 SNP were associated with higher sCTLA-4 levels (p

Objective Monocyte chemoattractant protein 1 (MCP-1) has been suggested to be involved in the pathophysiology of insulin resistance (IR); therefore, variants in the MCP-1 gene may contribute to the development of this disease. The aim of this study was to analyze the relationship of the -2518 A>G MCP-1 (rs1024611) gene polymorphism with insulin resistance in Mexican children. Subjects and methods A cross-sectional study was performed in 174 children, including 117 children without insulin resistance and 57 children with IR, with an age range of 6-11 years. Levels for serum insulin and high-sensitivity C-reactive protein were determined. The -2518 A>G MCP-1 polymorphism was identified by the polymerase chain reaction-restriction fragment length polymorphism method. Insulin resistance was defined as a HOMA-IR in the upper 75th percentile, which was ≥ 2.4 for all children. Results Genotype frequencies of the rs1024611 polymorphism for the insulin-sensitive group were 17% AA, 48% AG and 35% GG, and the frequency of G allele was 59%, whereas frequencies for the insulin-resistant group were 12% AA, 37% AG and 51% GG, and the frequency of G allele was 69%. The genotype and allele frequencies between groups did not show significant differences. However, the GG genotype was the most frequent in children with IR. The GG genotype was associated with insulin resistance (OR = 2.2, P = 0.03) in a genetic model. Conclusion The -2518 A>G MCP-1 gene polymorphism may be related to the development of insulin resistance in Mexican children.

The influence of genetic factors in rheumatoid arthritis (RA) has been described, including several cytokine genes such as transforming growth factor β (TGF-β) with regulatory effects on lymphocytes, dendritic cells, macrophages, chondrocytes, and osteoblasts, which are important in the RA pathogenesis. The G915C TGF-β1 polymorphism has been associated with soluble TGF-β1 (sTGF-β) serum levels. Thus, we studied the association of G915C (Arg25Pro) TGF-β1 polymorphism with sTGF-β1 serum levels in RA. We enrolled 120 RA patients and 120 control subjects (CS). The G915C TGF-β1 polymorphism was determined by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) method, and sTGF-β1 serum levels were quantified using an ELISA kit. The genotype frequency of G915C TGF-β1 polymorphism in RA and CS was G/G (91.7%), G/C (8.3%), C/C (0%) and G/G (85.8%), G/C (14.2%), C/C (0%), respectively, without significant differences. Moreover, the G/G TGF-β1 genotype carriers presented the highest disability index evaluated for the Spanish HAQ-DI score (P

We assessed whether the −844 G/A polymorphism and mRNA expression of plasminogen activator inhibitor 1 (PAI-1) gene are associated with rheumatoid arthritis (RA). Demographic data, hematological, biochemical parameters, disease activity–disability indexes, −844 G/A genotypes and mRNA expression levels of the PAI-1 gene were determined in 50 RA patients and 50 healthy subjects (HS). Non-significant differences in genotype and allele frequencies related to −844 G/A polymorphism in RA versus HS, were found. High mRNA expression of the PAI-1 gene, was demonstrated in RA versus HS (P < 0.05). In addition, A/A genotype carriers showed increase of PAI-1 mRNA expression (3.1-fold) respect to G/G and G/A genotypes in RA patients (P < 0.05). Our finding suggest an association of A/A −844 PAI-1 genotype with high PAI-1 mRNA expression in RA patients.

Introduction Inflammation and endothelial dysfunction are considered the primary manifestations of the cardiovascular disease. Studies have established a relationship among components of metabolic syndrome (MetS) with inflammatory markers and the loss of permeability, vasoconstriction and vasodilatation endothelial. Objective To determine the relationship among the concentrations of soluble endothelial dysfunction molecules and inflammation cytokines and components of the metabolic syndrome in young population. Material and methods A study was performed in 240 young adult students ages 18–28 years. To define the presence of clinical and metabolic alterations and MetS the modified ATP-III criteria was considered. In all subjects were determined sociodemographic characteristics, anthropometric measures and the metabolic profile. Circulating levels of MCP-1, VEGF-A, sICAM-1, sVCAM-1, sE-selectin and sVE-cadherin were determined by ELISA immunoassay (Bioscience). Statistical analysis was performed using STATA statistical software v. 9.2. Results From all the participants, 44.6% had obesity, 59.9% had abdominal obesity, 49.6% low HDL-c and 16.7% high levels triglycerids. The 16.25% of the population showed 3 or more components of the MetS. Elevated MCP-1, sICAM-1 and sE-selectin levels were linked to the presence of obesity. In a model adjusted by age–gender, high soluble levels of MCP-1 and VEGF-A were linked with abdominal obesity (OR = 1.83; 1.02–3.28 and OR = 2.03; 1.15–3.56, respectively), as well as to the presence of the 2 components of MetS. sVCAM-1 levels were associated with impaired glucose (OR = 4.74; 1.32–17.0); sE-selectin with low HDL-c (OR = 1.99; 1.05–3.75), although sICAM-1 and sVE-cadherin were associated with impaired systolic blood pressure (OR = 4.04; 1.24–13.1 and OR = 6.28; 1.90–20.7, respectively). Conclusion Levels of circulating MCP-1 and VEGF-A were associated with adiposity, levels of sVCAM-1 with the presence of impaired glucose, sE-selectin with low HDL-c, while the levels of sICAM-1 and sVE-cadherin were associated with impaired systolic blood pressure in young adults independently of other traditional risk factors.

Background Diet is an important environmental factor that interacts with genes to modulate the likelihood of developing disorders in lipid metabolism and the relationship between diet and genes in the presence of other chronic diseases such as obesity. The objective of this study was to analyze the interaction of a high fat diet with the APOA2 (rs3813627 and rs5082), APOA5 (rs662799 and rs3135506) and LEPR (rs8179183 and rs1137101) polymorphisms and its relationship with obesity and dyslipidemia in young subjects. Methods The study included 200 young subjects aged 18 to 25 years (100 normal-weight and 100 obese subjects). Dietary fat intake was measured using the frequency food consumption questionnaire. Genotyping of polymorphisms was performed by PCR-RFLP. Results Individuals carrying the APOA5 56 G/G genotype with a high saturated fatty acid consumption (OR = 2.7, p = 0.006) and/or total fat (OR = 2.4, p = 0.018), associated with an increased risk of obesity. We also found that A/G + G/G genotypes of the 668 A/G polymorphism in the LEPR gene with an intake ≥12 g/d of saturated fatty acids, have 2.9 times higher risk of obesity (p = 0.002), 3.8 times higher risk of hypercholesterolemia (p = 0.002) and 2.4 times higher risk of hypertriglyceridemia (p = 0.02), than those with an intake

Peptidyl arginine deiminase IV (PADI4) enzyme catalyzes the citrullination of proteins, which are recognized by anti-cyclic citrullinated peptide antibodies (anti-CCP) in rheumatoid arthritis (RA) patients. Here, we determined the association between PADI4 gene polymorphisms and haplotypes with RA susceptibility and clinical characteristics in a western Mexican population. The relationship of PADI4 polymorphisms with anti-CCP and PADI4 mRNA expression was also evaluated. PADI4_89, PADI4_90 and PADI4_92 polymorphisms were individually associated with RA susceptibility. The GTG haplotype was significantly associated with: RA susceptibility; disease onset at ≤ 40 years and anti-CCP antibodies. PADI4 expression was three fold higher in RA patients carrying the susceptibility haplotype (GTG) than in non-susceptibility haplotype carriers (ACC). In conclusion, polymorphisms and functional haplotype (GTG) in PADI4 are associated with RA susceptibility as well as anti-CCP antibodies in a Mexican population. This supports the role of PADI4 early in RA pathogenesis by promoting the generation of citrullinated autoantigens.

The human adenovirus 36 (Ad-36) is causally and correlatively associated in animals and humans, respectively, with increased adiposity and altered metabolic profile. In previous studies, the relationship between Ad-36 seropositivity with obesity was established in adults and children. We evaluated the association of positive antibodies to Ad-36 with obesity and metabolic profile in Mexican children. Seventy-five children with normal-weight and 82 with obesity were studied in this research. All children had a clinic assessment which included weight, height, body circumferences, and skinfold thickness. Laboratory analyzes included triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein, and glucose and insulin levels. An enzyme-linked immunosorbent assay (ELISA) was used to determine the antibodies to Ad-36 in the serum samples. The overall Ad-36 seroprevalence was 73.9%. Ad-36 seropositivity had a higher prevalence in obese children than in normal weight group (58.6 versus 41.4%,P=0.007). Ad-36 seropositivity was associated with obesity (OR=2.66,P=0.01) and high-density lipoprotein OR=2.85,P=0.03). The Ad-36 seropositive group had greater risk of 4 metabolic abnormalities compared with those children without none alteration. In summary, Ad-36 seropositivity was associated with obesity and low HDL-c levels in the sample of children studied.

Background and objective Childhood obesity is considered the main risk factor for the development of metabolic syndrome (MetS) during childhood, adolescence and adulthood. This study aimed to determine the prevalence of MetS components and its main defining combinations in a sample of school children with and without obesity. Patients and methods A total of 225 children aged 6–12 years, 106 obese and 119 with normal weight were included. MetS was defined by the presence of 3 or more of the following: obesity as a body mass index ≥ 95th percentile, fasting glucose ≥ 100 mg/dl, triglycerides ≥ 150 mg/dl, high density lipoproteins cholesterol (HDL-c) Results We found MetS components in both groups. Most frequent abnormalities in the obese group included increased levels of HDL-c, triglycerides, fasting glucose and total cholesterol, while increased levels of glucose and total cholesterol, and lower HDL-c levels predominated in the normal weight group. The prevalence of MetS in the obese group was 44.3% and, in normal weight children, it was 0.84%. The 3 main components that defined the MetS in the obese group were obesity/triglycerides/HDL-c (34.0%), obesity/glucose/triglycerides/HDL-c (29.8%) and obesity/glucose/HDL-c (14.9%), while the only combination observed in the normal weight group was glucose/HDL-c/triglycerides. Conclusion A percentage of 44.3 of obese school children had MetS, and dyslipidemia showed to be strong determinants of MetS. Although the prevalence of MetS was low in children with normal weight, one third of them showed one of the components of MetS.

We studied the association of age, gender, and distribution of body fat with prehypertension in a sample of Mexican adults. This study was performed in a sample of 900 adults (275 men and 625 women), with the median age of 42 years. Resting blood pressure was measured in duplicate, and prehypertension and hypertension were defined according to JNC 7 criteria. The prevalence of hypertension and prehypertension in our population was 11.56% and 26.5%, respectively. The prevalence of prehypertension was significantly higher in men than in women. Prehypertension was associated with middle and old age (odds ratio [OR] = 2.6 and 2.4, respectively, P < .001), abdominal obesity (OR = 1.3, P = .008), upper quintiles of body mass index (OR = 2.05, P = .005), waist (OR = 1.97, P = .01) and hip (OR = 2.04, P = .005) circumferences, and body fat (OR = 2.37, P = .001). The main factors associated with the development of prehypertension are age, central obesity, and body fat.

Knee osteoarthritis (OA) is a common chronic degenerative disease characterized by the loss of articular cartilage components due to an imbalance between extracellular matrix destruction and repair. The proinflammatory cytokines involved in OA, TNFα and IL1β, are considered the major implicated. The aim of this study was to investigate the relationship between TNFα −308 and −238 polymorphisms with messenger RNA (mRNA) and soluble TNFα expression in knee OA patients and healthy subjects (HS). Case–control study involved 50 knee OA patients classified according to 1986 ACR Classification Criteria, as well as 100 HS. The Western Ontario and McMaster Universities Osteoarthritis Index and Lequesne disability index were applied to OA patients. The −308 and −238 polymorphisms were determined by polymerase chain reaction–restriction fragment length polymorphism technique. The TNFα mRNA expression was quantified by real-time PCR using TaqMan method. The sTNFα levels were measured by enzyme-linked immunosorbent assay. The TNFα mRNA expression in knee OA patients was higher than in HS (1.56-fold). In addition, the TNFα mRNA expression was higher in carriers of G allele in the knee OA group for both polymorphisms. The sTNFα levels were increased in G/G versus G/A genotypes in both studied polymorphisms (p

Macrophage migration inhibitory factor (MIF) is an upstream pro-inflammatory cytokine that is associated with the pathogenesis of autoimmune inflammatory diseases including rheumatoid arthritis (RA). Two polymorphisms in the upstream region exist in the MIF gene and are associated with RA susceptibility or severity in different populations. In this case-control study, we investigated whether MIF polymorphisms are associated with RA susceptibility or activity in a western Mexican population .The relationship of MIF levels with clinical features of disease also was assessed. Genotyping of the -794 CATT5-8 (rs5844572) and the -173 G>C (rs755622) polymorphisms was performed by PCR and PCR-RFLP respectively on 226 RA patients and 210 healthy subjects. Serum MIF levels were determined by ELISA. We found a significant association between the -794 CATT5-8 6,7 MIF genotype with RA. Moreover, we detected an association between the -794 CATT7 allele with early onset RA. The -794 CATT7 and -173(*)C alleles, which are in linkage disequilibrium, were associated with high disease activity on RA patients. A positive correlation between circulating MIF levels and C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, anti-citrullinated protein/peptides antibodies and TNFα was detected. MIF levels appear to be associated with disease progression rather than disease activity, which is distinct from the established relationship between disease activity and TNFα levels. In conclusion, the MIF gene and protein are associated with RA in a western Mexican population, with a main contribution onto early onset and early stages of disease.

Objective. We evaluated the association between four polymorphisms in theCRPgene with circulating levels of C-reactive protein (CRP), type 2 diabetes (T2D), obesity, and risk score of coronary heart disease.Methods. We studied 402 individuals and classified them into four groups: healthy, obese, T2D obese, and T2D without obesity, from Guerrero, Southwestern Mexico. Blood levels of CRP, glucose, cholesterol, triglycerides, and leukocytes were measured. Genotyping was performed by PCR/RFLP, and the risk score for coronary heart disease was determined by the Framingham's methodology.Results. The TT genotype of SNP rs1130864 was associated with increased body mass index and T2D patients with obesity. We found that the haplotype 2 (TGAG) was associated with increased levels of CRP (β=0.3; 95%CI: 0.1, 0.5;P=0.005) and haplotype 7 (TGGG) with higher body mass index (BMI) (β=0.2; 95%CI: 0.1, 0.3;P<0.001). The risk score for coronary heart disease was associated with increased levels of CRP, but not with any polymorphism or haplotype.Conclusions. The association between the TT genotype of SNP rs1130864 with obesity and the haplotype 7 with BMI may explain how obesity and genetic predisposition increase the risk of diseases such as T2D in the population of Southwestern Mexico.

Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting the synovial membrane, cartilage and bone. PAI-1 is a key regulator of the fibrinolytic system through which plasminogen is converted to plasmin. The plasmin activates the matrix metalloproteinase system, which is closely related with the joint damage and bone destruction in RA. The aim of this study was to investigate the relationship between 4G/5G PAI-1 polymorphism with mRNA expression and PAI-1 plasma protein levels in RA patients. 113 RA patients and 123 healthy subjects (HS) were included in the study. The 4G/5G PAI-1 polymorphism was determined by polymerase chain reaction–restriction fragment length polymorphism method; the PAI-1 mRNA expression was determined by real-time PCR; and the soluble PAI-1 (sPAI-1) levels were quantified using an ELISA kit. No significant differences in the genotype and allele frequencies of 4G/5G PAI-1 polymorphism were found between RA patients and HS. However, the 5G/5G genotype was the most frequent in both studied groups: RA (42%) and HS (44%). PAI-1 mRNA expression was slightly increased (0.67 fold) in RA patients with respect to HS (P = 0.0001). In addition, in RA patients, the 4G/4G genotype carriers showed increased PAI-1 mRNA expression (3.82 fold) versus 4G/5G and 5G/5G genotypes (P = 0.0001), whereas the sPAI-1 plasma levels did not show significant differences. Our results indicate that the 4G/5G PAI-1 polymorphism is not a marker of susceptibility in the Western Mexico. However, the 4G/4G genotype is associated with high PAI-1 mRNA expression but not with the sPAI-1 levels in RA patients.

Background The Cytotoxic T lymphocyte antigen ( CTLA-4 ) is one of the major susceptibility genes associated with autoimmune diseases. Susceptibility to rheumatoid arthritis (RA) is determined by both environmental and genetic factors. The genetic contribution approaches 50–60%. The association between RA with the + 49A>G CTLA-4 polymorphism in the Mexican population was investigated. Methods The polymerase chain reaction–restriction fragment was used to amplify the + 49A>G CTLA-4 polymorphism in RA patients and healthy subjects (HS). Results We analyzed the association between the + 49A>G CTLA-4 polymorphism and RA. The G allele frequency was higher in RA patients than HS (46.8 vs 37.7%, OR = 1.45, p = 0.01). RA patients carrying the A/G genotype were significantly more likely to be positive to CRP and RF. There was no evidence of an association between SNP genotypes and the clinical characteristics of rheumatoid arthritis. Conclusions The + 49A>G CTLA-4 polymorphism is a genetic marker of susceptibility for RA in western Mexican population.

Background Previous studies have reported elevated levels of C-reactive protein (CRP) in obese and diabetic subjects, but it is unclear whether both these conditions have an additive effect on the variability of serum CRP levels. Methods and Results The study enrolled 385 men and women who were classified into 4 groups: (1) diabetes (n=97), (2) obesity (n=108), (3) diabetes/obesity (n=78), and (4) healthy (n=102). All were Mexican subjects from Guerrero State. Serum high-sensitivity CRP (hs-CRP) levels were higher in both type 2 diabetes mellitus (T2DM)/obesity and obesity (5.1 mg/L) groups than in the diabetics (1.8 mg/L) without obesity. Only the measurements of obesity were strongly related to hs-CRP (body mass index, r=0.46 and waist circumference, r=0.41). The presence of T2DM and obesity explain 20% of the circulating hs-CRP level, following waist circumference (16%), leukocyte count (10%), diastolic blood pressure (6%), and female gender (4%). Obese subjects (odds ratio (OR)=6.3) and T2DM/obesity patients (OR=6.9) showed high risk for coronary disease and this effect was increased in T2DM/obesity women (OR=9.9). Also, abdominal obesity was associated with high coronary disease risk (OR=5.4), showing an increase in women (OR=7.3). Conclusion High hs-CRP levels are related to obesity and central distribution of body fat, leading to a higher cardiovascular risk among Mexican subjects. (Circ J 2008; 72: 1170 - 1174)

Background Several association studies have shown that -844 G/A and HindIII C/G PAI-1 polymorphisms are related with increase of PAI-1 levels, obesity, insulin resistance, glucose intolerance, hypertension and dyslipidemia, which are components of metabolic syndrome. The aim of this study was to analyze the allele and genotype frequencies of these polymorphisms in PAI-1 gene and its association with metabolic syndrome and its components in a sample of Mexican mestizo children. Methods This study included 100 children with an age range between 6-11 years divided in two groups: a) 48 children diagnosed with metabolic syndrome and b) 52 children metabolically healthy without any clinical and biochemical alteration. Metabolic syndrome was defined as the presence of three or more of the following criteria: fasting glucose levels ≥ 100 mg/dL, triglycerides ≥ 150 mg/dL, HDL-cholesterol < 40 mg/dL, obesity BMI ≥ 95th percentile, systolic blood pressure (SBP) and diastolic blood pressure (DBP) ≥ 95th percentile and insulin resistance HOMA-IR ≥ 2.4. The -844 G/A and HindIII C/G PAI-1 polymorphisms were analyzed by PCR-RFLP. Results For the -844 G/A polymorphism, the G/A genotype (OR = 2.79; 95% CI, 1.11-7.08; p = 0.015) and the A allele (OR = 2.2; 95% CI, 1.10-4.43; p = 0.015) were associated with metabolic syndrome. The -844 G/A and A/A genotypes were associated with increase in plasma triglycerides levels (OR = 2.6; 95% CI, 1.16 to 6.04; p = 0.02), decrease in plasma HDL-cholesterol levels (OR = 2.4; 95% CI, 1.06 to 5.42; p = 0.03) and obesity (OR = 2.6; 95% CI, 1.17-5.92; p = 0.01). The C/G and G/G genotypes of the HindIII C/G polymorphism contributed to a significant increase in plasma total cholesterol levels (179 vs. 165 mg/dL; p = 0.02) in comparison with C/C genotype. Conclusions The -844 G/A PAI-1 polymorphism is related with the risk of developing metabolic syndrome, obesity and atherogenic dyslipidemia, and the HindIII C/G PAI-1 polymorphism was associated with the increase of total cholesterol levels in Mexican children.