Search

Background: C-reactive protein (CRP) is involved in inflammatory pathways that are associated with the onset and progression of type 2 diabetes mellitus (T2DM) as well as an increased risk of an ac...

Atherosclerosis plays an important role in the pathophysiology of acute coronary syndrome (ACS). CD36 is a scavenger receptor involved in lipid metabolism. Some single-nucleotide variants in the non-coding region could indirectly alter the expression and the function of the protein.The aim of this study was to investigate the gene and protein expression associated with CD36 variants (rs1194182;C G; rs1049654;C A, rs1334512;G T, and rs3211892;G A) in ACS patients from the western Mexican population.We recruited 310 ACS patients and 308 subjects in the control group (CG). Genotyping was determined by TaqMan SNP genotyping assays. CD36 expression at the mRNA level was quantified by TaqMan gene expression assays. Soluble CD36 (sCD36) was measured by enzyme-linked immunosorbent assay.We show that rs1194182G C variant provides a protective effect with a 1.7-fold lower susceptibility to develop ACS (p = 0.03); however, this association was masked by diabetes and dyslipidemia. We observed a higher sCD36 concentration in patient with ST-segment elevation myocardial infarction (STEMI) compared with patients with unstable angina (UA) (p = 0.038). Likewise, in diabetic patients versus non-diabetic (p 0.001). We observed in patients an increase in CD36 mRNA expression (1.91 times higher) than in the CG (p = 0.02).The rs1194182 seems to be associated with diabetes in a risky manner, in ACS patients and protective for dyslipidemia in both groups. The concentration of sCD36 seems to be associated with the clinical spectrum of the ACS patients and the presence of diabetes, since patients with STEMI present significantly elevated level compared with UA.

Basal cell carcinoma (BCC) is the most common dermatological neoplasms in Caucasian populations. In Mexico, a prevalence of 3.9 per 1000 habitants is estimated. Recently, the macrophage migration inhibitory factor (MIF) has been related to different types of cancer. Therefore, this study aimed to investigate the genetic association of haplotypes of [-794(CATT)5-8/-173G>C]MIF gene polymorphisms and its soluble levels in BCC. A total of 360 individuals were recruited for the study, that is, 180 of the total amounts were patients with BCC histologically confirmed and the remaining 180 individuals were identified as control subjects (CS). Both polymorphisms were genotyped by PCR and PCR-RFLP (restriction fragment length polymorphism), and MIF serum levels were measured by ELISA kit. A borderline difference was found between the 55 genotype and the susceptibility to BCC (5.6% vs 1.7% in BCC and CS, respectively, OR=3.7 and p=0.04). Furthermore, the haplotype 7G showed a significant association with BCC (p=0.02, OR=1.99). Concerning MIF soluble levels, patients with BCC showed a media of 2.1 ng/mL and CS showed 4.4 ng/mL, the comparison between groups was significant (p

Introduction. Multiple sclerosis is an inflammatory disease, where fibrin deposition and the impairment in its degradation have been shown to play an important role in the demyelination process. Tissue plasminogen activator (tPA) is a serine protease that enhances the conversion of plasminogen into its active form plasmin, the principal tPA inhibitor is the PAI-1. Several PAI-1 polymorphisms impact its gene expression and protein activity. Furthermore, the aim of this study was to investigate the association between the - 844 G>A, HindIII C>G, and 4G/5G PAI-1 polymorphisms and susceptibility to MS. Material and Methods. The study group included 400 Mexican mestizo subjects: 200 unrelated patients and 200 unrelated individuals identified as control subjects. The analysis of PAI-1 polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism. Results. A significant association was found between the CG genotype of the HindIII C>G PAI-1 polymorphism and susceptibility to MS (OR=1.58, p=0.03); moreover, the frequency of 5G allele and 5G/5G genotype of the 4G/5G PAI-1 polymorphism was statistically significant (OR=1.36 and p=0.04 and OR=2.43 and p=0.02, respectively). With respect to the relation between the scores of progression (EDSS) and severity (MSSS), no association was found between EDSS and genotypes of the PAI-1 polymorphisms analyzed. Regarding MSSS, male that carries genotype GA of the -844 G>A and genotype 4G/5G of the 4G/5G PAI-1 polymorphisms showed a significant association with an increase of media of MSSS in comparison with females (p=0.01 in both cases).

Background and aim Presence of metabolic syndrome (MS) in patients with type 2 diabetes mellitus (T2DM) involves an increased risk of cardiovascular disease and death. Markers such as ApoB/ApoA1 and non-HDL-cholesterol/HDL-cholesterol ratios have been used to predict this risk with conflicting results. The study objective was to establish the relationship between the apoB/apoA1 and non-HDL-cholesterol/HDL-cholesterol ratios and MS in T2DM patients from a Madrid (Spain) district. Patients and methods One hundred patients with T2DM who attended University Hospital Infanta Leonor (Vallecas, Madrid, Spain) between January 2014 and June 2017 were enrolled. A blood sample was taken every 6 months from all patients to measure the different lipid parameters and to calculate ApoB/ApoA1 and non-HDL-cholesterol/HDL-cholesterol ratios. A Mann–Whitney's U test to compare means and a Spearman's correlation test for correlations between variables were used, and a multivariate regression analysis was performed to determine the association between MS and the ApoB/ApoA1 and non-HDL-cholesterol/HDL-cholesterol ratios. Values of p Results Associations were found between MS and ApoA1 (R2 = 0.164, p = 0.028), ApoB/ApoA1 (R2 = 0.187, p = 0.001), and non-HDL-cholesterol/HDL-cholesterol (R2 = 0.269, p = 0.0001) ratios and, in women with MS, between ApoB/ApoA1 ratio and ischemic cardiomyopathy (IC) (R2 = 0.160, p = 0.032). Associations remained after adjusting for comorbidities and risk factors. Conclusions In the T2DM patients studied, MS was independently associated to ApoA1 and the ApoB/ApoA1 and non-HDL-cholesterol/HDL-cholesterol ratios. Both ratios were better predictors of MS in T2DM subjects that its components alone. The ApoB/ApoA1 ratio could be used as a cardiovascular risk marker in women with MS.

The current global prevalence of heart failure is estimated at 64.34 million cases, and it is expected to increase in the coming years, especially in countries with a medium-low sociodemographic index where the prevalence of risk factors is increasing alarmingly. Heart failure is associated with many comorbidities and among them, cancer has stood out as a contributor of death in these patients. This connection points out new challenges both in the context of the pathophysiological mechanisms involved, as well as in the quality of life of affected individuals. A hallmark of heart failure is chronic activation of the renin-angiotensin-aldosterone system, especially marked by a systemic increase in levels of angiotensin-II, a peptide with pleiotropic activities. Drugs that target the renin-angiotensin-aldosterone system have shown promising results both in the prevention of secondary cardiovascular events in myocardial infarction and heart failure, including a lower risk of certain cancers in these patients, as well as in current cancer therapies; therefore, understanding the mechanisms involved in this complex relationship will provide tools for a better diagnosis and treatment and to improve the prognosis and quality of life of people suffering from these two deadly diseases.

Basal cell carcinoma (BCC) is the most common dermatological neoplasms in Caucasian populations. In Mexico, a prevalence of 3.9 per 1000 habitants is estimated. Recently, the macrophage migration inhibitory factor (MIF) has been related to different types of cancer. Therefore, this study aimed to investigate the genetic association of haplotypes of [-794(CATT)5-8/-173GC]MIF gene polymorphisms and its soluble levels in BCC. A total of 360 individuals were recruited for the study, that is, 180 of the total amounts were patients with BCC histologically confirmed and the remaining 180 individuals were identified as control subjects (CS). Both polymorphisms were genotyped by PCR and PCR-RFLP (restriction fragment length polymorphism), and MIF serum levels were measured by ELISA kit. A borderline difference was found between the 55 genotype and the susceptibility to BCC (5.6% vs 1.7% in BCC and CS, respectively, OR=3.7 and p=0.04). Furthermore, the haplotype 7G showed a significant association with BCC (p=0.02, OR=1.99). Concerning MIF soluble levels, patients with BCC showed a media of 2.1 ng/mL and CS showed 4.4 ng/mL, the comparison between groups was significant (p0.01). Our findings suggest that the 55 genotype and the haplotype 7G are associated with the susceptibility to BCC; furthermore, a significant difference was found between MIF soluble levels in both study groups.

Introduction and Objective. In Mexico, there has been an increase in the risk of cardiovascular disease due to rising life expectancy, westernized lifestyle, lack of prevention, and industrialized exposure. This article describes the pharmacological treatment, surgical interventions, and associated clinical complications in patients diagnosed with acute coronary syndrome (ACS) and their impact on in-hospital mortality frequency in a Cardiology Unit in Instituto Mexicano del Seguro Social. Methods. This is a retrospective study including male and female patients aged ≥18 years who were diagnosed with ACS. The collected data included demographic characteristics, risk factors, medications, electrocardiograms, surgical procedures, and in-hospital deaths. Results. There are at least 20% more diagnoses of ST-segment elevation myocardial infarction in this hospital compared to the latest national reports in Mexico. The most common risk factors were type 2 diabetes mellitus, hypertension, smoking, and dyslipidaemia. Diabetic patients with a clinical history of percutaneous coronary intervention had a higher risk of non-ST-segment elevation myocardial infarction than nondiabetics (OR: 2.34; p=0.013), also smoking patients with previous heart surgery than nonsmokers (OR: 7.73; p=0.0007). The average in-hospital mortality was 3.6% for ACS. Conclusions. There is a higher percentage of coronary interventionism and improvement in pharmacological treatment, which is reflected in lower mortality. The substantial burden of T2DM could be related to a higher number of cases of STEMI. Diabetics with precedent percutaneous coronary intervention and smokers with previous heart surgery have an increased risk of subsequent infarction.

Acute coronary syndrome (ACS) is the leading cause of death in elderly patients worldwide. Due its participation in apoptosis, fibrosis, and angiogenesis, transforming growth factor-β (TGF-β) isoforms had been categorized as risk factors for cardiovascular diseases. However, due their contradictory activities, a cardioprotective role has been suggested. The aim was to measure the plasma levels of TGF-β1, 2, and 3 proteins in patients with ACS. This was a case-control study including 225 subjects. The three activated isoforms were measured in serum using the Bio-Plex Pro TGF-β assay by means of magnetic beads; the fluorescence intensity of reporter signal was read in a Bio-Plex Magpix instrument. We observed a significant reduction of the three activated isoforms of TGF-β in patients with ACS. The three TGF-β isoforms were positively correlated with each other in moderate-to-strong manner. TGFβ-2 was inversely correlated with glucose and low-density lipoprotein (LDL)-cholesterol, whereas TGF-β3 was inversely correlated with the serum cholesterol concentration. The production of TGF-β1, TGF-β2, and TGF-β3 are decreased in the serum of patients with ACS. Further follow-up controlled studies with a larger sample size are needed, in order to test whether TGF-β isoforms could be useful as biomarkers that complement the diagnosis of ACS.

Resumen Antecedentes y objetivo Las alteraciones en el metabolismo de los lipidos contribuyen al sindrome coronario agudo (SCA). Se ha demostrado que los polimorfismos rs670, rs5070 y rs693 modifican el riesgo de enfermedad cardiovascular. La apolipoproteina A- I (ApoA- I ) desempena un papel principal en el transporte inverso del colesterol; la apolipoproteina B (ApoB) contribuye a la acumulacion de colesterol en la placa. El objetivo de este estudio fue investigar la asociacion entre los polimorfismos rs670 y rs5070 de APOA1 y el polimorfismo rs693 de APOB con SCA y los niveles circulantes de estas proteinas, e investigar si ApoB/ApoA- I podria introducirse como parametro independiente predictor de riesgo de la enfermedad cardiovascular y como biomarcador del tratamiento de reduccion de lipidos en la poblacion mexicana. Metodos Se incluyo a 300 pacientes con SCA y 300 sujetos control (SC). Resultados Ni las frecuencias genotipicas ni las alelicas de los polimorfismos rs670, rs5070 y rs693 reflejaron diferencias estadisticamente significativas entre los grupos. Los niveles sericos de ApoA- I (195 frente a 161,4 mg/dl; p I (varones: 176,3 mg/dl; mujeres: 209,1 mg/dl). Conclusion Los polimorfismos rs670, rs5070 y rs693 no constituyen factores de susceptibilidad genetica para SCA en la poblacion de Mexico y no tienen efecto sobre las concentraciones de sus apolipoproteinas. En nuestra poblacion, ApoA- I , ApoB y c-HDL podrian constituir unos mejores biomarcadores del riesgo cardiovascular, y podrian indicar si las dosis de estatinas reducen debidamente las particulas aterogenicas.

The CD40/CD40L system is a binding key for co-stimulation of immune cells. Soluble form of CD40L has been widely studied as marker of inflammatory and autoimmune diseases. Here we analyze serum concentrations of sCD40L, as well as 14 cytokines, in patients with Multiple Sclerosis (MS) treated with Glatiramer acetate or Interferon beta. In the healthy control group, we found in serum a highly positive correlation between sCD40L and Interleukin (IL)-31, an anti-inflammatory Th2 cytokine. Additionally, an important reduction in IL-31 and sCD40L serum levels, as well as a significant reduction in CD40 mRNA expression and complete depletion of CD40L mRNA, detected from peripheral blood cells, was found in treated patients with MS. Therefore, sCD40L and IL-31 must be taken into account as possible prognostic markers when analyzing the disease progress of MS in order to provide more personalized treatment.

The objective of this study was to determine the association of the CD40LG 3′-UTR (CA)n microsatellite with rheumatoid arthritis (RA) and CD40LG mRNA levels in females from western Mexico. A case-control study with 219 RA patients and 175 control subjects (CS) was conducted. Genotyping was performed by polymerase chain reaction (PCR), X 2 test was used to compare genotype and allele frequencies, and odds ratios and 95% confidence intervals were calculated to evaluate the association between RA and the microsatellite. CD40LG mRNA expression was assessed by real-time quantitative PCR. For comparisons between groups, Kruskal-Wallis or Mann-Whitney U tests for non-parametric data and ANOVA test for parametric data were performed. Among the 13 different alleles identified, CA25 was the most represented (45.4% RA and 46.3% CS). Stratification according to CA repeats as CA25 showed a tendency towards a higher frequency of >CA25 alleles in RA patients (29%) compared to CS (23.4%). There was no association between any genotype and the clinical parameters of RA patients. According to the 2-∆∆Cq method, CD40LG mRNA expression in RA patients was 4.5-fold higher compared to CS; this difference was significant when assessed by the 2-∆Cq method (p = 0.028). Compared to carriers of the CA25/CA25 genotype, CS carrying the CA25/>CA25 carriers. The 3′-UTR CD40LG (CA)n microsatellite is not a genetic marker for RA in western Mexican population; however, results suggest that it plays a role in the CD40LG mRNA expression.

Rheumatoid arthritis (RA) is a common autoimmune disease with a complex genetic background. The peptidyl arginine deiminase type IV (PADI4) gene has been associated with RA susceptibility in several populations. We addressed the relationship between three exonic PADI4 gene single nucleotide polymorphisms (SNPs) PADI4_89 (rs11203366), PADI4_90 (rs11203367) and PADI4_92 (rs874881) and related haplotypes with RA in a population from Southern México. This study included 200 RA patients and 200 control subjects. The SNPs were evaluated using the polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) technique, and antibodies to cyclic citrullinated peptides (anti-CCP) were measured by enzyme-linked immunosorbent assay (ELISA). In this population, the minor alleles of PADI4_89∗G, PADI4_90∗T and PADI4_92∗G gene polymorphisms were associated with RA susceptibility (OR=1.34, p=0.04; OR=1.35, p=0.03; OR=1.34, p=0.04; respectively). The GTG haplotype was also significantly associated with RA (OR=2.27 95%CI=1.18-4.41; p=0.008), but did not show association with levels of anti-CCP antibodies and clinical parameters. In conclusion, our replication study in a Southern Mexican population suggests that PADI4 individual polymorphisms and the related susceptibility haplotype (GTG) are also genetic risk markers for RA.

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.

Resumen Introduccion y objetivos El gen de la proteina tirosina fosfatasa no receptora de tipo 22 (PTPN22) codifica la proteina linfoide tirosina fosfatasa –Lyp–, un importante regulador negativo de la activacion de celulas T, que se ha asociado a distintos trastornos autoinmunitarios. El polimorfismo −1123G > C en el gen PTPN22 parece afectar al control de la transcripcion de este gen, pero hasta la fecha, la importancia biologica sobre su contribucion al riesgo de desarrollar artritis reumatoide (AR) sigue siendo desconocida. En el presente estudio evaluamos la asociacion del polimorfismo −1123G > C con anti-cyclic citrullinated protein antibodies (anti-CCP, «anticuerpos antipeptido citrulinado ciclico») y el riesgo de desarrollar AR en la poblacion del occidente de Mexico. Materiales y metodos Se realizo un estudio transversal analitico, en el que participaron 300 pacientes con AR clasificados de acuerdo con los criterios del ACR-EULAR y 300 sujetos control (SC). El polimorfismo −1123 G > C se genotipifico mediante PCR-RFLP. Los niveles de anticuerpos anti-CCP fueron cuantificados mediante una prueba de ELISA. Resultados Encontramos una mayor prevalencia de genotipos homocigotos CC en SC en comparacion con los pacientes con AR (OR 0,41; intervalo de confianza del 95% 0,24-0,71; p = 0,001), lo que demuestra un posible efecto protector contra la AR. En cuanto a los niveles de anti-CCP, los portadores del genotipo CC mostraron los niveles mas bajos en el grupo de AR (p Conclusion El genotipo CC del polimorfismo −1123G > C en el gen PTPN22 es un factor protector para la AR en la poblacion mestiza mexicana y se asocia con niveles bajos de anticuerpos anti-CCP.

Acute coronary syndrome (ACS) can be triggered by the presence of inflammatory factors which promote the activation of immune cells by costimulatory molecules such as CD40 and its ligand CD40L. Environmental and genetic factors are involved in the etiology of the ACS. The aim of this study was to explore the gene and protein expression associated with CD40 and CD40L genetic variants in ACS patients from the western Mexican population. A total of 620 individuals from western Mexico were recruited: 320 ACS patients and 300 individuals without a history of ischemic cardiopathy were evaluated. The genotype was determined using TaqMan SNP genotyping assays. CD40 and CD40L expressions at the mRNA level were quantified using TaqMan Gene Expression Assays. Soluble protein isoforms were measured by enzyme-linked immunosorbent assay. We did not find evidence of association between CD40 (rs1883832, rs4810485, and rs11086998) and CD40L (rs3092952 and rs3092920) genetic variants and susceptibility to ACS, although rs1883832 and rs4810485 were significantly associated with high sCD40 plasma levels. Plasma levels of sCD40L can be affected by gender and the clinical spectrum of acute coronary syndrome. Our results do not suggest a functional role of CD40 and CD40L genetic variants in ACS. However, they could reflect the inflammatory process and platelet activation in ACS patients, even when they are under pharmacological therapy. Due to the important roles of the CD40-CD40L system in the pathogenesis of ACS, longitudinal studies are required to determine if soluble levels of CD40 and CD40L could be clinically useful markers of a recurrent cardiovascular event after an ACS.

Objective: The present study was specifically designed to discern the possible existence of subgroups of patients with the relapsing-remitting form of multiple sclerosis (RRMS) depending on their gender, age, disease stage (relapsing or remitting), time of disease evolution and response to different treatments. Methods: We analyzed samples from patients with RRMS (50 females and 32 males) and healthy individuals (25 matched for age and gender) and determined serum concentrations of IFN-γ, IL-10 and IL-17A. We stratified patients by gender, age, treatment and disease evolution time, and subsequently correlated these independent variables with the concentrations of the previously mentioned cytokines. Results: We provided initial evidence that treatment exerted possible differential effects depending on the time of disease duration. Results evidence the existence of different subgroups of patients with MS, who can be classified as follows: (a) male or female under or over 40 years of age; (b) disease duration according to treatment (under or over 8 years of disease); (c) classification according to fluctuating levels of IFN-γ, IL-10 and IL-17A in the following three stages of disease evolution: 10 years. Conclusion: These subgroups must be taken into account for the clinical follow-up of patients with MS in order to provide them with a better and more personalized treatment, and also for a deep and detailed analysis of progressive disease, in an attempt to comprehend fluctuations and clinical variability by means of a better understanding of intrinsically physiological variables of the disease.

BACKGROUND Macrophage migration inhibitory factor (MIF) is an immunoregulatory cytokine that plays a crucial role as a regulator of the innate and adaptive immune responses and takes part in the destructive process of the joint in rheumatoid arthritis (RA) by promoting angiogenesis and inducing proinflammatory cytokines and matrix metalloproteinases (MMP). We evaluated if recombinant human MIF (rhMIF) induces the production of TNF-α, IFN-γ, IL-1β, IL-6, IL-10, IL-17A, and IL- 17F in peripheral blood mononuclear cells (PBMC) from RA patients and control subjects (CS). METHODS The PBMC from RA patients and CS were stimulated for 24 hours with combinations of LPS, rhMIF or the MIF antagonist ISO-1. Cytokine profiles were measured using a multiplex immunoassay and, macrophage migration inhibitory factor (MIF) was determined by ELISA kit. RESULTS The PBMC of CS and RA produced Th1 and Th17 cytokines under stimulation with rhMIF, however, this effect was higher in the cells of RA patients. The rhMIFstimulated PBMC from RA patients produced higher levels of Th1 and Th17 cytokines in comparison with unstimulated cells: TNF-α (538.81 vs. 5.02 pg/mL, p

BACKGROUND: Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by destruction of exocrine glands as a result of T and B cells infiltrated in glandular tissue. CD28 and CTLA‐4 play a crucial role in T cell activation and inhibition. The aim of this study was to associate CD28 and CTLA4 haplotypes with susceptibility to pSS in patients from western Mexico. METHODS: Polymerase chain reaction and restriction fragment length polymorphism were performed to identify CD28 and CTLA4 genotypes in 111 patients with pSS and 138 control subjects (CS). Haplotype analysis was carried out by SHEsis program. Soluble serum levels of CD28 (sCD28) and CTLA‐4 (sCTLA‐4) were quantified by ELISA kit. RESULTS: The CD28 GC haplotype was associated with low risk to pSS (2.5‐folds, P T, +49 A>G, and +6230 G>A, or their haplotypes did not show any difference. CONCLUSION: Our findings suggest that CD28 GC,CTLA4 CAG, and CGA haplotypes are associated with susceptibility to pSS in patients from western Mexico. It seems that genetic control of CD28 and CTLA4 as well as local immune response in glandular tissue may regulate the impact of the gene expression in pSS. It is necessary to confirm this hypothesis in an integrative study.

Acute coronary syndrome (ACS) describes any condition characterized by myocardial ischaemia and reduction in blood flow. The physiopathological process of ACS is the atherosclerosis where MIF operates as a major regulator of inflammation. The aim of this study was to assess the mRNA expression of MIF gene and its serum levels in the clinical manifestations of ACS and unrelated individuals age- and sex-matched with patients as the control group (CG). All samples were run using the conditions indicated in TaqMan Gene Expression Assay protocol. Determination of MIF serum levels were performed by enzyme-linked immunosorbent assay and MIF ELISA Kit. ST-segment elevation myocardial infraction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) showed 0.8 and 0.88, respectively, less expression of MIF mRNA with regard to CG. UA and STEMI presented more expression than NSTEMI 5.23 and 0.68, respectively. Otherwise, ACS patients showed significant higher MIF serum levels (p=0.02) compared with CG. Furthermore, the highest soluble levels of MIF were presented by STEMI (11.21 ng/dL), followed by UA (10.34 ng/dL) and finally NSTEMI patients (8.75 ng/dL); however, the differences were not significant. These novel observations further establish the process of MIF release after cardiovascular events and could support the idea of MIF as a new cardiac biomarker in ACS.

Primary Sjogren’s syndrome (pSS) is an autoimmune disease characterized by lymphocytic infiltration of salivary and lacrimal glands. Interleukin-10 (IL-10) plays a role in autoimmune diseases by promoting B-cell activation and autoantibodies production. IL10 -1082A > G, -819C > T, -592C > A polymorphisms and their haplotypes have been associated with IL-10 production. The aim of this study was to associate IL10 haplotypes with mRNA expression and soluble IL-10 levels with susceptibility to pSS in 111 Mexican patients and 111 healthy subjects (HS). Primary Sjogren’s syndrome patients showed high levels of sIL-10 ( p = 0.0001 vs HS) correlating with anti-Ro and anti-La antibodies ( p IL10 mRNA expression in pSS was higher than HS (0.8 vs 0.1, p = 0.1537). However, no difference was observed in sIL-10 levels between haplotypes. Patients carriers of GCC haplotype showed higher mRNA expression than ACC + ATA (1.4 vs 0.6, p = 0.2424) and high foci number ( p = 0.04 vs ACC). Our results suggest a strong relationship of IL10 with pSS which is demonstrated by the increased mRNA expression and also high sIL-10 levels positively correlated with autoantibodies. Besides that, the GCC haplotype carriers expressed high mRNA. However, IL10 haplotypes were not associated with sIL-10 in pSS from Western Mexico which suggest that diverse biological factors may regulate the IL10 expression in pSS.

Background. Acute coronary syndrome (ACS) has an important impact in public health with high morbidity and mortality. Prothrombotic and proinflammatory states are involved in the pathogenesis of the disease. Plasminogen activator inhibitor-1 (PAI-1) is the major inhibitor of the fibrinolysis and also is part of immune response. The -844 G>A gene polymorphism is related to increased PAI-1 protein levels. The aim of the study is to evaluate the association of -844 G>A PAI-1 polymorphism with ACS.Methods. A total of 646 individuals were recruited from Western Mexico: 350 unrelated healthy subjects and 296 patients with diagnosis of ACS.Results. The most important risk factor in our population was hypertension, followed by smoking. The genetic distribution showed an association of the A allele (OR=1.27,P=0.04) and AA genotype (OR=1.86,P=0.02) with ACS. The recessive model displayed similar results (OR=1.76,P=0.02). As additional finding, we observed significant differences in the genetic distribution of ACS dyslipidemic patients (OR=1.99,P=0.04). The A allele and AA genotype of -844 polymorphism of PAI-1 gene are risk factors for ACS. The AA genotype might be associated with the development of dyslipidemia in ACS patients.

Lipid metabolism alterations contribute to acute coronary syndrome (ACS). rs670, rs5070 and rs693 polymorphisms have shown to modify the risk of cardiovascular disease. Apolipoprotein A-I (ApoA-I) plays a major role in reverse cholesterol transport; apolipoprotein B (ApoB) contributes to accumulation of cholesterol in the plaque. The aim of this study was to investigate the association of rs670 and rs5070 polymorphisms of APOA1 and rs693 polymorphism of APOB with ACS and circulating levels of its proteins and find if ApoB/ApoA-I could be implemented as an independent parameter of risk for cardiovascular disease and as a biomarker of lipid-lowering therapy effectiveness in Mexican population.Three hundred patients with ACS and 300 control subjects (CS) were included.Neither genotype nor allele frequencies of rs670, rs5070 and rs693 polymorphisms showed statistical differences between groups. Serum levels of ApoA-I (195 vs. 161.4mg/dL; P.001) and ApoB (167 vs. 136.9mg/dL; P.001) were significantly higher in CS compared with ACS; however, there was no genetic association. Unstable angina patients showed the highest ApoA-I levels (males: 176.3mg/dL; females: 209.1mg/dL).The rs670, rs5070 and rs693 polymorphisms are not genetic susceptibility factors for ACS in Mexican population and had no effect on their apolipoprotein concentrations. In our population, ApoA-I, ApoB and HDL-C could be better biomarkers of cardiovascular risk and could indicate if statins doses reduce atherogenic particles properly.

L-selectin gene (SELL) is a candidate gene for the development of acute coronary syndrome (ACS) that contributes to endothelial dysfunction. The -642CT (rs2205849) and 725CT (rs2229569) polymorphisms have been associated with changes in gene expression, ligand affinity and increased risk of cardiovascular disease. The aim of this study was to investigate the association between the haplotypes constructed with the -642CT and 725CT polymorphisms of the SELL gene, the expression levels of its mRNA and the serum levels of soluble L-selectin with ACS.We recruited 615 individuals of Mexican origin matched by age, including 342 patients with ACS and 273 individuals without personal history of ischemic cardiopathy as control group (CG). Genotyping was performed by PCR-RFLP. The qPCR technique was used to analyze the expression of mRNA using TaqMan® UPL probes. The levels of soluble L-selectin were measured with ELISA.The allele variants in both polymorphisms were over-represented in the CG compared to the ACS (OR range: 0.371-0.716, p0.006). The CT and TT haplotypes had a protective effect against the development of ACS (OR=0.401, p0.0001; OR=0.628, p0.0001, respectively). SELL expression was 3.076 times higher in the ACS group compared to CG (p0.001). The levels of soluble L-selectin were similar between ACS and CG.Both polymorphisms had no effect on mRNA expression and soluble protein levels. The polymorphisms -642CT and 725CT of the SELL gene are protective factors against the development of ACS. There is an increased gene expression of L-selectin in ACS compared to CG in the population of Western Mexico.

Acute coronary syndrome (ACS) is considered one of the main causes of death worldwide. Contradictory findings concerning the impact of the angiotensin-converting enzyme (ACE) gene on cardiovascular diseases have been reported. Previous conclusions point out that the variability in results depends on ethnicity and genetic polymorphisms to determine the association of rs4340 polymorphisms of the ACE gene and ACE circulating levels in ACS. Genotyping of rs4340 polymorphisms was performed in a total of 600 individuals from Western Mexico divided into two groups: the ACS and the control group (CG). The polymorphisms were identified by polymerase chain reaction. Serum ACE concentration was determined by enzyme-linked immunosorbent assay. D/D carriers had higher ACE levels than I/I carriers (3.6 vs 2.8 ng/mL, P < 0.0021) in the CG. The D/D genotype of the rs4340 polymorphism is associated with higher ACE concentration levels; however, the polymorphism was not associated with ACS.

Introduction. The acute coronary syndrome (ACS) is a complex disease where genetic and environmental factors are involved.E-selectingene is a candidate for ACS progression due to its contribution in the inflammatory process and endothelial function. The rs5361 (561A>C) polymorphism in theE-selectingene has been linked to changes in gene expression, affinity for its receptor, and plasmatic levels; therefore it is associated with an increased risk of cardiovascular disease. The aim of this study was to determine the association of the rs5361 polymorphism with ACS and to measure serum levels of soluble E-selectin (sE-selectin).Materials and Methods. 283 ACS patients and 205 healthy subjects (HS) from Western Mexico were included. The polymerase chain reaction-restriction fragment length polymorphism was used to determine the rs5361 polymorphism. The sE-selectin levels were measured by enzyme-linked immunosorbent assay.Results. Neither genotype nor allele frequencies of the rs5361 polymorphism showed statistical differences between groups. The sE-selectin levels were significantly higher in ACS patients compared to HS (54.58 versus 40.41 ng/ml,P=0.02). The C allele had no effect on sE-selectin levels.Conclusions. The rs5361E-selectingene polymorphism is not a susceptibility marker for ACS in Western Mexico population. However, sE-selectin may be a biological marker of ACS.

Polymorphisms in the FTO gene are associated with obesity, body mass index, hip circumference, and visceral and subcutaneous fat area. The objective of this study was to analyze the association of the FTO rs17817449 genetic variant (T>G polymorphism) with body fat distribution patterns in women. We included 65 women and 71 healthy subjects in this study. Anthropometric parameters were determined and laboratory studies were performed. The polymorphism was detected by a PCR-RFLP method. The groups were categorized by type of body fat distribution: gynoid (N = 29) and android (N = 36). We found that the FTO gene polymorphism was not associated with body fat distribution according to the type of obesity (P > 0.05). The contribution of G and T alleles among groups indicated no statistically significant differences between the reference and gynoid group [P = 0.93; odds ratio (OR) = 0.97; 95% confidence interval (CI) = 0.46-2.02] and the reference and android group (P = 0.56; OR = 1.20; 95%CI = 0.54-2.82). Thorax circumference and thorax breast circumference were significantly different between the two groups (P = 0.009 and 0.021, respectively) with the genotype TT. We conclude that the FTO rs17817449 TT genotype predisposes individuals to fat deposition in the thoracic and breast region; individuals carrying this genotype had a decrease in thoracic and breast dimensions indirectly causing the gynoid phenotype in Mexican women.

Fabry disease (FD) is an X-linked lysosomal storage disease caused by α-galactosidase A deficiency; in contrast to other X-linked diseases, heterozygous females can be as affected as men. The construction and analysis of a family pedigree is a powerful tool to aid clinicians in diagnosis, establishment of inheritance pattern, and early detection of potentially affected relatives. The present study highlights the importance of pedigree analysis in families with FD for identifying other possibly affected relatives and investigating the clinical manifestations. This clinical report included 12 Mexican index cases with confirmed FD diagnosis. We constructed and analyzed their pedigree, and diagnosed FD in 24 affected relatives. Clinical features were similar to those reported for other populations. Pedigree analysis further identified an additional 30 women as possible carriers. We conclude that pedigree construction and analysis is a useful tool to help physicians detect and diagnose relatives at risk for FD, particularly heterozygous females, so that they can receive genetic counseling and early treatment. Mexican families with FD were similar to other populations reported in the literature, and our findings confirmed that heterozygous females can have signs and symptoms ranging from subtle manifestations to the classical severe presentation described in males.

Basal cell carcinoma (BCC) is the dermatological neoplasm more prevalent worldwide, in recent years there has been an increase in the number of cases becoming a health problem. Despite its high incidence, there is little information about genetic factors that lead to the carcinogenesis of this neoplasms. In the last years, macrophage migration inhibitory factor (MIF) has received particular attention, its expression has been linked to the development of different types of cancer. Therefore, the aim of this study was to investigate the genetic association of −794 CATT5–8 and −173 G>C MIF polymorphisms with BCC. A total of 150 BCC patients and 150 individuals with similar age than cases as a control group were recruited. Total genomic DNA was extracted from peripheral blood leukocytes by the salting out method. The −794 CATT5–8 MIF polymorphism was analyzed by conventional PCR and polyacrylamide gel electrophoresis, the −173 G>C MIF polymorphism was genotyped by PCR-RFLP as was done in previous studies by our research group. It was found that BCC incidence is higher in women than men additionally the localization of this neoplasia are more prevalent in head and neck. Also, it was found that the 5/5 genotype of the −794 CATT5–8 MIF polymorphisms of confers a risk to BCC development (OR=4.55, p=0.04). Respect to the −173 G>C MIF polymorphism we did not find a statistical difference. In conclusion, our findings suggest that the 5/5 genotyope of −794 CATT5–8 MIF polymorphism is associated with the development of BCC in patients from western Mexico. Further studies are needed due to the relation of the functions of MIF and de development of cancer.

Acute coronary syndrome (ACS) belongs to the clinical entities characterized by obstruction of a coronary artery. In its etiology, inflammation contributes significantly trough the activation of immune cells by co-stimulatory molecules as CD40 and CD40L. The purpose of this work was to explore the changes of mRNA and circulating soluble levels of CD40-CD40L in ACS patients and association with genetic variants in a western Mexican population. 320 ACS patients and 300 individuals with similar age than cases without ischemic cardiopathy were recruited. Genotype determination was made using TaqMan SNP genotyping assays. CD40 and CD40L mRNA expression in whole blood samples were quantified using TaqMan Gene Expression Assays. Soluble levels were measured in plasma by enzyme-linked immunosorbent assay. We did not find evidence of association between on CD40 (rs1883832, rs4810485 and rs11086998) and CD40L (rs3092952 and rs3092920) genetic variants and susceptibility to ACS nor changes in their mRNA expression (p>0.05), although rs1883832 and rs4810485 affected significantly sCD40 circulating levels (p=0.005; p=0.015, respectively). Circulating soluble levels were higher in ACS patients; specifically sCD40L was higher in male patients with unstable angina compared to female patients (p=0.016). Our results showed genetic variants affect soluble levels of CD40 although the CD40 and CD40L polymorphisms are not associated with susceptibility to ACS in western Mexican population. CD40L mRNA expression, sCD40 and sCD40L plasma levels were higher in ACS patients even when they are under pharmacological treatment, which suggests an active role of the CD40-CD40L system in the immunopathogenesis of acute coronary syndrome.

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

Background. Leprosy is a debilitating infectious disease of human skin and nerves. Genetics factors of the host play an important role in the disease susceptibility. Toll-interacting protein (TOLLIP) is an inhibitory adaptor protein within the toll-like receptor (TLR) pathway, which recognizes structurally conserved molecular patterns of microbial pathogens, initiating immune responses. The objective of this study was to investigate the association of variants in theTOLLIPgene with susceptibility to leprosy in Mexican patients.Methods.TOLLIPpolymorphisms were studied using a case-control design of Mexican patients with lepromatous leprosy (LL). The polymorphisms ofTOLLIPat loci −526 C>G (rs5743854), 1309956C>T (rs3750920), 1298430C>A (rs5744015), and 1292831 G>A (rs3750919) were analyzed by PCR, with sequence-specific primers in LL patients and healthy subjects (HS) as controls.Results. Genotype distributions were in Hardy Weinberg equilibrium for all sites except for rs3750920. Neither genotype nor allele frequencies were statistically different between LL patients and controls (P>0.05). The maximum pairwise D’ coefficient reached was 0.44 of linkage (P=0.01) for all the polymorphisms except for rs5743854. The three loci haplotype comparison yielded no significant differences between groups.Conclusions. Just the individuals with genotype C/C of rs3750920 have a trend of protective effect to developing LL.

Recombination patterns can be indirectly inferred by means of linkage disequilibrium (LD) estimates, since LD is negatively correlated with genetic distance. However, LD does not necessarily have absolute correspondence with genetic distance. We estimated LD at 5 loci located in the 21q22.3 region. These STRs (D21S1440, D21S168, D21S1260, D21S1446, and D21S1411) covered 8.81 Mb of the 21q22.3 region. They were genotyped by conventional PCR. Similar size samples previously validated by sequencing were used as a genotyping control. Three hundred and sixty-nine individuals (62 families) living in Guadalajara, Mexico, were included. As an inclusion criterion, each family had a positive paternity test by autosomal markers for the CODIS core loci. Two hundred and thirty phase known haplotypes were identified by familial segregation. Only those haplotypes whose frequency was higher than 4% were taken into account for LD estimation, expressed as Lewontin's D' coefficient and Bonferroni's correction P values. For all 5 loci, the genetic distributions were in agreement with Hardy-Weinberg expectations. Heterozygosity and haplotype diversity were ≥ 0.69 and 99.58%, respectively. D21S1440-D21S168 (4.51 cM) and D21S1446-D21S1411 (4.58 cM) marker haplotype frequencies were significantly different from those expected by random distribution. The remaining haplotypes, including those with minimal inter-distance (D21S1260-D21S1446, 1.44 Mb), did not show LD. The 5 STRs at the 21q22.3 region in this Mexican population showed a non-homogeneous LD pattern, which demonstrates that recombination or linkage should not be assumed solely on the basis of genetic distance.