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Introduction: Polymorphisms in the CETP gene promoter have been associated with cardiovascular risk and lipid alterations; however, their role in the development of hypertension has not been extens...

Background: Adiponectin, encoded by the ADIPOQ gene, is produced mainly by adipose tissue, and meaning as a metabolic and immunological regulator. The polymorphism rs822396 in ADIPOQ gene was previ...

Colorectal cancer is the third cause of cancer and the second leading cause of death worldwide. The CD44 gene plays a key role in malignant processes, including growth, survival, epithelial to mesenchymal transition and metastasis. It is also known that some variants as rs187116 (c.67+4883G>A) and rs7116432 (c.2024+779A>G) can modulate the function of the CD44 gene and malignant transformation in several neoplasms. This study aims to explore, for the first time, the association of the CD44 rs187116 and rs7116432 variants in patients with colorectal cancer. Genomic DNA from 250 patients and 250 healthy blood donors were analyzed. The identification of variants was made by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Association was calculated by the odds ratio (OR) test and multivariate analysis. Individuals carrying the G/A and A/A genotypes for the rs187116 polymorphism showed an increased risk for colorectal cancer (OR = 3.11, 95% CI: 1.87-5.16, P = 0.001 and OR = 3.59, 95% CI: 2.06-6.25, P = 0.001, respectively). After adjusting for age and gender, these same genotypes and the G/G genotype of the rs7116432 polymorphism were associated with TNM stage and tumor location in the colon. Moreover, the A-G (rs187116 and rs7116432) haplotype was associated with increased risk; while, the haplotype G-A (rs187116 and rs7116432) was related with decreased risk. In conclusion, our results suggest that the here analyzed CD44 variants are involved with risk, TNM stage and tumor location in colorectal cancer.

Spinocerebellar ataxia type 10 (SCA10) is characteri- zed by ataxia, psychiatric disorders convulsions, and locus at 22q13.311. It is caused by expansions between 800-4500 pentanucleotide ATTCT repeats in intron 9 of the ATXN10 gene1-2. The ATXN10 gene encodes ataxin-10 protein (known as E46L) involved in neuritogenesis 1. SCA10 has a founder origin in Mexican, Brazilian, Argentine populattons but is rare in others.

The genetic makeup of Indigenous populations inhabiting Mexico has been strongly influenced by geography and demographic history. Here, we perform a genome-wide analysis of 716 newly genotyped individuals from 60 of the 68 recognized ethnic groups in Mexico. We show that the genetic structure of these populations is strongly influenced by geography, and our demographic reconstructions suggest a decline in the population size of all tested populations in the last 15–30 generations. We find evidence that Aridoamerican and Mesoamerican populations diverged roughly 4–9.9 ka, around the time when sedentary farming started in Mesoamerica. Comparisons with ancient genomes indicate that the Upward Sun River 1 (USR1) individual is an outgroup to Mexican/South American Indigenous populations, whereas Anzick-1 was more closely related to Mesoamerican/South American populations than to those from Aridoamerica, showing an even more complex history of divergence than recognized so far., Indigenous populations, including in those in Mexico are underrepresented in genetic studies. Here, the authors perform a population genetics study of indigenous peoples in Mexico to explore demographic histories of the region in the context of geography and cultural influences.

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of death worldwide. The named "destruction complex" has a critical function in the Wnt/β-catenin pathway regulating the level of β-catenin in the cytoplasm and nucleus. Alterations in this complex lead to the cellular accumulation of β-catenin, which participates in the development and progression of CRC. This study aims to determine the contribution of polymorphisms in the genes of the β-catenin destruction complex to develop CRC, specifically adenomatous polyposis coli (APC) (rs11954856 G>T and rs459552 A>T), axis inhibition protein 1 (AXIN1) (rs9921222 C>T and rs1805105 C>T), AXIN2 (rs7224837 A>G), and dishevelled 2 (DVL2) (2074222 G>A and rs222836 C>T). Genomic DNA from 180 sporadic colorectal cancer patients and 150 healthy blood donors were analyzed. The identification of polymorphisms was made by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) methodology. Association was calculated by the odds ratio (OR) test. Increased susceptibility to CRC was associated with the polymorphic variants rs11954856 (APC), rs222836 (DVL2), and rs9921222 (AXIN1). Decreased susceptibility was associated with the polymorphisms rs459552 (APC) and 2074222 (DVL2). Association was also observed with advanced Tumor-Node-Metastasis (TNM) stages and tumor location. The haplotypes G-T in APC (rs11954856-rs459552) and A-C in DVL2 (rs2074222-rs222836) were associated with decreased risk of CRC, while the G-T haplotype in the DVL2 gene was associated with increased CRC risk. In conclusion, our results suggest that variants in the destruction complex genes may be involved in the promotion or prevention of colorectal cancer.

The coronavirus disease 2019 (COVID-19) pandemic has become a serious global health problem and numerous studies are currently being conducted to improve understanding of the components of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, as well as to identify solutions that mitigate the effects of COVID-19 symptoms. The nutritional supplement Vita Deyun® is composed of silymarin, glutathione, vitamin C and selenium. Studies of its individual components have demonstrated their benefits as anti-inflammatory agents, antioxidants and enhancers of the immune response. Therefore, the present study aimed to evaluate the in vitro effects of Vita Deyun on the expression of angiotensin-converting enzyme 2 (ACE2) in diverse cell lines, as well as in the presence or absence of the SARS-CoV-2 open reading frame (ORF)3a protein. Through reverse transcription-quantitative PCR, the use of viral particles containing SARS-CoV-2 ORF3a and bioinformatics analysis via the National Center for Biotechnology Information databases, ACE2 was determined to be highly expressed in oral and skin epithelial cells, with a lower expression observed in lung cells. Notably, the expression of SARS-CoV-2 ORF3a increased the level of ACE2 expression and Vita Deyun treatment diminished this effect. In addition, Vita Deyun treatment markedly decreased interleukin-18 mRNA levels. The combination of phytonutrients in Vita Deyun may help to boost the immune system and could reduce the effects of COVID-19. Ongoing clinical studies are required to provide evidence of the efficacy of Vita Deyun.

Colorectal cancer is the third cause of cancer and the second leading cause of death worldwide. The CD44 gene plays a key role in malignant processes, including growth, survival, epithelial to mesenchymal transition and metastasis. It is also known that some variants as rs187116 (c.67+4883GA) and rs7116432 (c.2024+779AG) can modulate the function of the CD44 gene and malignant transformation in several neoplasms. This study aims to explore, for the first time, the association of the CD44 rs187116 and rs7116432 variants in patients with colorectal cancer. Genomic DNA from 250 patients and 250 healthy blood donors were analyzed. The identification of variants was made by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Association was calculated by the odds ratio (OR) test and multivariate analysis. Individuals carrying the G/A and A/A genotypes for the rs187116 polymorphism showed an increased risk for colorectal cancer (OR = 3.11, 95% CI: 1.87-5.16, P = 0.001 and OR = 3.59, 95% CI: 2.06-6.25, P = 0.001, respectively). After adjusting for age and gender, these same genotypes and the G/G genotype of the rs7116432 polymorphism were associated with TNM stage and tumor location in the colon. Moreover, the A-G (rs187116 and rs7116432) haplotype was associated with increased risk; while, the haplotype G-A (rs187116 and rs7116432) was related with decreased risk. In conclusion, our results suggest that the here analyzed CD44 variants are involved with risk, TNM stage and tumor location in colorectal cancer.

The spinocerebellar ataxia type 2 is a neurodegenerative disease with autosomal dominant inheritance; clinically characterized by progressive cerebellar ataxia, slow ocular saccades, nystagmus, ophthalmoplegia, dysarthria, dysphagia, cognitive deterioration, mild dementia, peripheral neuropathy. Infantile onset is a rare presentation that only has been reported in four instances in the literature. In the present work a boy aged 5 years 7 months was studied due to horizontal gaze-evoked nystagmus, without saccades, ataxic gait, dysarthria, dysphagia, dysmetria, generalized spasticity mainly pelvic, bilateral Babinsky. The mother aged 27 years-old presented progressive cerebellar ataxia, dysarthria, dysmetria, dysdiadochokinesis, limb ataxia and olivopontocerebellar atrophy. The molecular analysis was made by identifying the expansion repeats in tandem by long PCR to analyze the repeats in the ATXN2 gene. We found an extreme CAG expansion repeats of ~884 repeats in the child. We describe a Mexican child affected by SCA2 with an infantile onset, associated with a high number of CAG repeats previously no reported and anticipation phenomenon.

Background: Non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease in adolescents, is a feature of metabolic syndrome (MetS). Obesity and insulin resistance (IR) are risk factors for NAFLD, as well as inflammation-related genetic markers. The relationship between metabolic or inflammation-related genetic markers and alanine aminotransferase (ALT) is not fully understood. We examined the relationship of MetS, metabolic and inflammation-related genetic markers with elevated ALT in adolescents. Methods: A total of 674 adolescents participated in a cross-sectional study in Guadalajara, Mexico. Elevated ALT (>40 IU/L), a surrogate marker of NAFLD, and MetS (International Diabetes Federation definition) were evaluated. Obesity, IR, lipids, C-reactive protein (CRP) and genetic markers (TNFA-308G>A, CRP+1444C>T, IL1RN and IL6-597/-572/-174 haplotype) were evaluated. Multivariate logistic regression was performed. Results: Elevated ALT was observed in 3% and 14.1% (total and obese, respectively) of the adolescents. Obesity (odds ratio [OR], 5.86; 95% confidence interval [95% CI], 1.16–25.89), insulin (OR, 8.51; 95% CI, 2.61–27.71), IR (OR, 9.10; 95% CI, 2.82–29.38), total cholesterol (TC) (OR, 3.67; 95% CI, 1.25–10.72), low-density lipoprotein-cholesterol (LDL-C) (OR, 3.06; 95% CI, 1.06–8.33), non-high-density lipoprotein-cholesterol (HDL-C) (OR, 3.88; 95% CI, 1.27–11.90) and IL1RN (OR, 4.64; 95% CI, 1.10–19.53) were associated with elevated ALT. Among males, ≥2 MetS criteria were associated with elevated ALT (OR, 4.22; 95% CI, 1.14–15.71). Conclusions: Obesity, insulin, IR, high TC, high LDL-C, high non-HDL-C and IL1RN polymorphism were associated with elevated ALT. Among males, ≥2 MetS criteria were associated with elevated ALT. There is an urgent need to reduce obesity and IR in adolescents to prevent NAFLD.

Summary Interferon‐inducible transmembrane protein 3 (IFITM3) participates in the defense against viral infections. This study identified and compared the frequency of the IFITM3 rs12252 polymorphism in 410 individuals in western Mexico. The western Mexican allelic frequencies (frequency of the “C” allele = 0.18) differ from some American, East Asian and European populations.

Gestational diabetes mellitus (GDM) is a metabolically complex disease with major genetic determinants. GDM has been associated with insulin resistance and dysfunction of pancreatic beta cells, so the GDM candidate genes are those that encode proteins modulating the function and secretion of insulin, such as that for calpain 10 (CAPN10). This study aimed to assess whether single nucleotide polymorphism (SNP)-43, SNP-44, SNP-63, and the indel-19 variant, and specific haplotypes of the CAPN10 gene were associated with gestational diabetes mellitus. We studied 116 patients with gestational diabetes mellitus and 83 women with normal glucose tolerance. Measurements of anthropometric and biochemical parameters were performed. SNP-43, SNP-44, and SNP-63 were identified by polymerase chain reaction (PCR)-restriction fragment length polymorphisms, while the indel-19 variant was detected by TaqMan qPCR assays. The allele, genotype, and haplotype frequencies of the four variants did not differ significantly between women with gestational diabetes mellitus and controls. However, in women with gestational diabetes mellitus, glucose levels were significantly higher bearing the 3R/3R genotype than in carriers of the 3R/2R genotype of the indel-19 variant (p = 0.006). In conclusion, the 3R/3R genotype of the indel-19 variant of the CAPN-10 gene influenced increased glucose levels in these Mexican women with gestational diabetes mellitus.

Polymorphisms in the LEP (G–2548A and A19G), LEPR (A326G, A668G and G3057A) and RETN (C–420G and G+62A) genes were documented according to their association with alterations in biochemical parameters such as glucose, insulin and lipid profiles, along with serum leptin and resistin concentrations. The aim of the study was to establish any contribution of the G-2548A and A19G polymorphisms of the LEP gene, the A326G, A668G and G3057A polymorphisms of the LEPR gene, and the C-420G and G+62A polymorphisms of the RETN gene to serum leptin and resistin levels in Mexican young adults. Clinical and biochemical variables, serum leptin and resistin levels, and genotype profiles were analysed in 66 Mexican young adults. Seven polymorphisms in the LEP, LEPR and RETN genes were genotyped using polymerase chain reaction–restriction fragment length polymorphisms analysis. Individuals carrying allele 3057A of the G3057A polymorphism in the LEPR gene showed significantly higher leptin concentrations than those bearing the genotype G/G (43.78 ± 39.11 vs 28.20 ± 14.12 ng/mL; p = 0.021). There were no associations of serum leptin or resistin levels according to the genotype of the other six analysed polymorphisms. Our results suggest that the allele 3057A of the LEPR G3057A polymorphism contributes to increased serum leptin levels in Mexican young adults.

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of death worldwide. The named "destruction complex" has a critical function in the Wnt/β-catenin pathway regulating the level of β-catenin in the cytoplasm and nucleus. Alterations in this complex lead to the cellular accumulation of β-catenin, which participates in the development and progression of CRC. This study aims to determine the contribution of polymorphisms in the genes of the β-catenin destruction complex to develop CRC, specifically adenomatous polyposis coli (APC) (rs11954856 GT and rs459552 AT), axis inhibition protein 1 (AXIN1) (rs9921222 CT and rs1805105 CT), AXIN2 (rs7224837 AG), and dishevelled 2 (DVL2) (2074222 GA and rs222836 CT). Genomic DNA from 180 sporadic colorectal cancer patients and 150 healthy blood donors were analyzed. The identification of polymorphisms was made by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) methodology. Association was calculated by the odds ratio (OR) test. Increased susceptibility to CRC was associated with the polymorphic variants rs11954856 (APC), rs222836 (DVL2), and rs9921222 (AXIN1). Decreased susceptibility was associated with the polymorphisms rs459552 (APC) and 2074222 (DVL2). Association was also observed with advanced Tumor-Node-Metastasis (TNM) stages and tumor location. The haplotypes G-T in APC (rs11954856-rs459552) and A-C in DVL2 (rs2074222-rs222836) were associated with decreased risk of CRC, while the G-T haplotype in the DVL2 gene was associated with increased CRC risk. In conclusion, our results suggest that variants in the destruction complex genes may be involved in the promotion or prevention of colorectal cancer.

Achondrogenesis is a skeletal dysplasia characterized primarily by short stature, severe micromelia, short and narrow chest, prematurity, polyhydramnios, fetal hydrops, and in utero or neonatal death. Based on the radiological and histopathological findings, there are three types of achondrogenesis: type 1A (Houston-Harris), type 1B (Fraccaro) and type 2 (Langer-Saldino).A premature female product was studied whose clinical, radiological and histopathological characteristics were compatible with achondrogenesis Type 1A. The family information allowed us to conclude that the 4 products of the 6 previous pregnancies were affected. Statistical analysis in at least 4 families previously described, including this family case showed significant differences between expected and observed number of members, being incongruent with an autosomal recessive mode of inheritance previously reported.therefore, it could be considered a new subtype of achondrogenesis type 1A due to the presence of a preferential germline mutation.La acondrogénesis es una displasia esquelética que se caracteriza principalmente por talla baja, micromelia grave, tórax corto y estrecho, prematurez, polihidramnios, hidropesía fetal y muerte fetal in utero o neonatal. Según los hallazgos radiológicos e histopatológicos existen tres tipos de acondrogénesis: tipo 1A (Houston-Harris), tipo 1B (Fraccaro) y tipo 2 (Langer-Saldino).Se sometió a estudio a un producto femenino prematuro cuyas características clínicas, radiológicas e histopatológicas fueron compatibles con acondrogénesis tipo 1A. La información familiar permitió concluir que los cuatro productos de los seis embarazos previos se encontraban afectados. El análisis estadístico en por lo menos cuatro familias previamente descritas, incluyendo este caso familiar, mostró diferencias significativas entre el número de miembros esperado y el observado, siendo incongruente con el modo de herencia autosómico recesivo previamente reportado.Podría considerarse un nuevo subtipo de acondrogénesis tipo 1A debida a la presencia de una mutación germinal preferencial.

Background Achondrogenesis is a skeletal dysplasia characterized primarily by short stature, severe micromelia, short and narrow chest, prematurity, polyhydramnios, fetal hydrops, and in utero or neonatal death. Based on the radiological and histopathological findings, there are three types of achondrogenesis: type 1A (Houston-Harris), type 1B (Fraccaro) and type 2 (Langer-Saldino). Clinical case A premature female product was studied whose clinical, radiological and histopathological characteristics were compatible with achondrogenesis Type 1A. The family information allowed us to conclude that the 4 products of the 6 previous pregnancies were affected. Statistical analysis in at least 4 families previously described, including this family case showed significant differences between expected and observed number of members, being incongruent with an autosomal recessive mode of inheritance previously reported. Conclusions therefore, it could be considered a new subtype of achondrogenesis type 1A due to the presence of a preferential germline mutation.

El gen de la ataxina-2 es un blanco en la patogénesis de enfermedades complejas, entre ellas los factores de riesgo cardiovascular y enfermedades neurodegenerativas. El gen ATXN2 tiene un VNTR en el exón 1, cuya expansión por encima de las 30 repeticiones provoca al desarrollo de ataxia espinocerebelosa tipo 2; las repeticiones en rango menor se asocian con diabetes tipo 2 o esclerosis lateral amiotrófica. También este locus está ligado con fenotipos metabólicos e inflamatorios. En conclusión, el gen puede ser utilizado como marcador clínico de fenotipos metabólicos y neurológicos, lo cual está relacionado con su efecto pleiotrópico.The ataxin 2 gene is a target in the pathogenesis of complex diseases, including cardiovascular risk factors and neurodegenerative diseases. ATXN2 gen has VNTR in exon 1, whose expansion exceeding 30 repetitions leads to the development of spinocerebellar ataxia type 2; lower-range repetitions are associated with type 2 diabetes or amyotrophic lateral sclerosis. This locus is also linked with metabolic and inflammatory phenotypes. In conclusion, this gene can be used as a clinical marker of metabolic and neurological phenotypes, which is related to its pleiotropic effect.

Mutations and polymorphisms of the GSK3β gene have been associated with several diseases including Alzheimer disease, diabetes and cancer; however, to date, no variants of this gene have been associated with colorectal cancer (CRC). This study aims to explore, for the first time, the association of the GSK3β rs334558 and rs6438552 polymorphisms with CRC.Genomic DNA from 330 CRC patients and healthy blood donors were analyzed. Identification of polymorphisms was made by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Association was calculated by the odds ratio (OR) test.Patients carrying the C/T genotype for the rs334558 (TC) polymorphism showed an increased risk for CRC (OR = 1.71, 95% CI: 1.05-2.79, P = 0.039); this association was also observed for TNM stage and tumor location. For the rs6438552 (TC) polymorphism, the OR analysis showed that patients carrying C/T and C/C genotypes have a decreased risk for CRC (OR = 0.44, 95% CI: 0.27-0.70, P = 0.001 and OR = 0.24, 95% CI: 0.10-0.64, P = 0.001, respectively); this decreased risk was also evident in the stratified analysis by TNM stage and tumor location. Haplotype analysis of these 2 loci of GSK3β (rs334558 and rs6438552) showed differential distribution. The T-T and C-C haplotype was associated with a decreased risk of CRC, while the T-C haplotype was associated with an increased risk of CRC.Our results denote that GSK3β gene polymorphisms play a significant role in promoting or preventing CRC. Additionally, variations in this gene are associated with the tumor site and the tumor-node-metastasis (TNM) stage in these patients.

Polymorphisms in the CYP2C9 and CYP2C19 genes confer potential risk for specific adverse drug reactions and therapeutic effect failure. Their frequencies differ among ethnic groups. This study was aimed to describe the distribution of CYP2C9 and CYP2C19 alleles and haplotypes in four Mestizo populations from Western Mexico and their comparison with the reported data from other ethnic groups.The CYP2C alleles (CYP2C9*2, CYP2C9*3, CYP2C19*2, and CYP2C19*3) were genotyped using polymerase chain reaction-restriction fragment length polymorphisms analyses using DNA samples from 477 healthy Mestizo individuals of Colima (n = 100), Jalisco (n = 147), Michoacán (n = 117), and Nayarit (n = 113).Frequencies ranged from 2.2-3.0% and 4.8-8.9% for CYP2C9*3 and CYP2C9*2 alleles, respectively, and 5.4-12.0% for CYP2C19*2, whereas the CYP2C19*3 allele was not found. Haplotype GACA, which harbors the loss-of-function allele CYP2C19*2, was the second most frequent (8.7%). Genetic heterogeneity between the Western Mexican populations studied here and the global population was evident (p 0.05), except for most American populations and other Mexican Mestizo populations.Our findings increase the evidence for genetic variability at relevant pharmacogenetic loci and could be useful in association studies involving drugs that are substrates for CYP2C enzymes in the Western Mexican population.

Objective To explore the clinical prognostic factors for adults affected with astrocytoma. Patients and methods Using a historic cohort, we selected 155 clinical files from patients with astrocytoma using simple randomization. The main outcome variable was overall survival time. To identify clinical prognostic factors, we used bivariate analysis, Kaplan Meier, the log rank test and the Cox regression models. The number of lost years lived with disability (DALY) based on prevalence, was calculated. Results The mean age at diagnosis was 45.7 years. Analysis according to tumour stage, including grades II, III and IV, also showed a younger age of presentation. Kaplan-Meier survival estimates showed that tumour grade, Karnofsky status (KPS) ≥70, resection type, chemotherapy, radiotherapy, alcohol consumption, familial history of cancer and clinical presentation were significantly associated with survival time. Using a proportional hazard model, age, grade IV, resection, chemotherapy + radiotherapy and KPS were identified as prognostic factors.The amount of life lost due to premature death in this population was 28 years. Conclusion In our study, astrocytoma was diagnosed in young adults. The overall survival was 15 months, 9% (n = 14) of patients presented a survival of 2 years, and 3% of patients survived 3 years. On average the number of years lost due to premature death and disability was 28.53 years.

The Interleukin (IL)-1 family of cytokines plays a key role in the inflammatory response. Genes coding for IL-1α, IL-1β, and IL-1Ra are located together as a block gene known as the IL-1 cluster. This genomic region shows wide nucleotide variability, and some polymorphisms have been widely studied and associated with features related to the metabolic syndrome.Eight polymorphisms within three genes of the IL-1 cluster, including IL1A (rs3783553, rs17561, and rs1800587), IL1B (rs1143634, rs1143627, and rs16944) and IL1RN (rs419598 and rs2234663) were genotyped in 460 Mexican adolescents. Genotype and haplotype frequencies are reported, as well as the linkage disequilibrium analysis. Genetic associations with some anthropometric and metabolic traits were evaluated.Allele frequencies were similar to those found in other populations, and genotype proportions were according to the Hardy-Weinberg equilibrium. Seven haplotypes were observed at frequencies ≥5%. Of the entire cluster, only the rs17561-rs1800587 and rs1143627-rs16944 pairs showed highest and significant linkage disequilibrium values. An haplotype of IL1A, rs17561T-rs1800587T, was significantly associated with increase in body mass index in males (p0.008), whereas IL1B and IL1RN variants showed associations with insulin, and hs-CRP (p0.05).Some MetS parameters seem to be influenced by variations in the IL-1 gene cluster in Mexican adolescents. These variations may confer risk for metabolic alterations from early ages, and and these risks may be different when variables such as sex are considered. Strategies leading to generate protective behaviors could be designed to take into account specific variations in the IL-1 gene cluster and biological conditions such as sex.

The physiopathology of rheumatoid arthritis (RA) is mediated by proinflammatory cytokines, some of which are regulated by the JAK/STAT pathway. Tofacitinib is a JAK inhibitor, but its role in the regulation of microRNAs (miRNAs) is unknown. There is also no information regarding the role of miRNAs in the clinical relapse/remission of RA. The present project aims to identify a signature profile of miRNA expression in a subgroup of RA patients who had to discontinue tofacitinib treatment (because of the ending of a 5-year open-label clinical trial) and to describe the expression of miRNAs during RA remission or flare-up. The relative expression of 61 miRNAs was determined in serum samples with the Firefly™ BioWorks assay. Statistical analysis was performed by means of Student's t-test and heatmap analysis was performed with Firefly™ Analysis Workbench software and in the software GraphPad® Prism v5.0. Target prediction and Gene Ontology analysis were carried out using bioinformatic tools. We found a distinctive signature of miRNA expression associated with relapse, featuring upregulated expression of hsa‑miR‑432‑5p (p 0.05). We also found upregulation of hsa‑miR‑194‑5p (p 0.05) in samples of patients with RA flare-up. Gene Ontology analysis of the target genes for hsa‑miR‑432‑5p was performed to identify relevant pathways associated with relapse; the implications of these pathways in the physiopathology of RA are discussed. Tofacitinib treatment does not have a direct effect on the expression of measured miRNAs. The changes in hsa‑miR‑432‑5p and hsa‑miR‑194‑5p are associated with the regulation of proinflammatory pathways and RA flare-up.

Bone disease in rheumatoid arthritis (RA) is a complex phenomenon where genetic risk factors have been partially evaluated. The system formed by receptor activator for nuclear factor-κB (RANK), receptor activator for nuclear factor-κB ligand (RANKL), and osteoprotegerin (OPG): RANK/RANKL/OPG is a crucial molecular pathway for coupling between osteoblasts and osteoclasts, since OPG is able to inhibit osteoclast differentiation and activation. We aim to evaluate the association between SNPs C950T (rs2073617), C209T (rs3134069), T245G (rs3134070) in theTNFRSF11B(OPG) gene, and osteoporosis in RA. We included 81 women with RA and 52 healthy subjects in a cross-sectional study, genotyped them, and measured bone mineral density (BMD) at the lumbar spine and the femoral neck. Mean age in RA was50±12with disease duration of12±8years. According to BMD results, 23 (33.3%) were normal and 46 (66.7%) had osteopenia/osteoporosis. We found a higher prevalence of C allele for C950T SNP in RA. Polymorphisms C209T and T245G did not reach statistical significance in allele distribution. Further studies including patients from other regions of Latin America with a multicenter design to increase the sample size are required to confirm our findings and elucidate if C950T SNP could be associated with osteoporosis in RA.

Background Polycystic ovary syndrome is a complex and heterogeneous disease leading to reproductive, as well as metabolic problems. It has been suggested that there may be a genetic predisposition in the aetiology of polycystic ovary syndrome. The identification of calpain 10 gene (CAPN10) as the first candidate gene for type 2 diabetes mellitus has focused the interest in investigating their possible connection with the polycystic ovary syndrome. This syndrome is associated with hyperinsulinaemia and insulin resistance, two metabolic abnormalities associated with type 2 diabetes mellitus. Objective To investigate if there is association between the SNP-63 and the genetic variant indel-19 of CAPN10 gene and polycystic ovary syndrome in women of reproductive age. Material and methods This study included 101 women (55 with polycystic ovary syndrome and 46 without polycystic ovary syndrome). The genetic variant indel-19 was identified by electrophoresis of the amplified fragments by PCR, and the SNP-63 by PCR-RFLP. Results The allele and genotype frequencies of the two variants do not differ significantly between women with polycystic ovary syndrome and the control women group. The haplotype 21 (defined by the insertion allele of indel-19 variant and C allele of SNP-63) was found with higher frequency in both study groups, being more frequent in the polycystic ovary syndrome patients group, however, this difference was not statistically significant. Conclusions The results suggest that SNP-63 and indel-19 variant of CAPN10 gene do not represent a risk factor for polycystic ovary syndrome in our patient group.

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PPARD encodes for peroxisome proliferator-activated receptor delta, which plays a significant role in controlling lipid metabolism, atherosclerosis, inflammation, cancer growth, progression, and apoptosis. Accumulated evidence suggests that the polymorphism rs2016520 in PPARD is associated with lipid metabolism, obesity, metabolic syndrome, and type 2 diabetes mellitus. The aim of this study was to determine whether the single nucleotide polymorphism +294T/C (rs2016520) in PPARD is associated with colorectal cancer (CRC) in the Mexican population. Genomic DNA from 178 CRC patients and 97 healthy blood donors was analyzed. The polymorphism was identified by the polymerase chain reaction-restriction fragment length polymorphism method. Results demonstrated that patients with the T/C genotype for the +294T/C (rs2016520) polymorphism present a protective role against CRC [odds ratio (OR) = 0.39; 95% confidence interval (CI) = 0.22-0.69; P = 0.0008]. This association was also evident for the T/C genotype in the stratified analysis by tumor-node-metastasis stages I+II (OR = 0.26, P = 0.0332) and III+IV (OR = 0.44, P = 0.0067). However, in the stratified analysis by tumor location, we observed an increased risk of rectal cancer (OR = 7.57, P = 0.0403) vs colon cancer (OR = 4.87, P = 0.234) in patients carrying the C/C genotype and under the dominant and recessive models of inheritance. In conclusion, for the first time, the association between the +294T/C (rs2016520) polymorphism and colorectal cancer has been studied in Mexican patients. Our results reveal that variations in PPARD may play a significant role in genetic susceptibility to colorectal cancer.

The so-called tumor necrosis factor (TNF) block includes the TNFA, lymphotoxin alpha and beta (LTA and LTB) genes with single-nucleotide polymorphisms (SNP) and microsatellites with an allele frequency that exhibits interpopulation variability. To date, no reports have included both SNPs and microsatellites at the TNF block to study Mestizo or Amerindian populations from Mexico. In this study, samples of five Mexican Mestizo populations (Durango, Guadalajara, Monterrey, Puebla, and Tierra Blanca) and four native-Mexican populations (North Lacandonians, South Lacandonians, Tepehuanos, and Yaquis) were genotyped for two SNPs (LTA+252A>G and TNFA-308G>A) and four microsatellites (TNFa, d, e, and f), to analyze the genetic substructure of the Mexican population. Allele and haplotype frequencies, linkage disequilibrium (LD), and interpopulation genetic relationships were calculated. There was significant LD along almost all of the TNF block but the lowest D' values were observed for the TNFf-TNFd pair. Mestizos showed higher allele and haplotype diversity than did natives. The genetic differentiation level was reduced among Mestizos; however, a slightly, but significant genetic substructure was observed between northern and southern Mexican Mestizos. Among the Amerindian populations, the genetic differentiation level was significantly elevated, particularly in both North and South Lacandonians. Furthermore, among Southern Lacandonians, inhabitants of Lacanja town were the most differentiated from all the Mexicans analyzed. The data presented here will serve as a reference for further population and epidemiological studies including these TNF polymorphisms in the Mexican population.

Objectives Mexico harbours a very complex genetically diverse population composed of two main groups: Mexican Mestizos and at least 68 heterogeneous native Mexican populations. CYP2C9 and CYP2C19 polymorphisms may confer risk for specific adverse drug reactions and therapeutic effect failure, and their frequencies exhibit ethnic variability. We aimed to describe the distribution of CYP2C9 and CYP2C19 alleles and haplotypes in four Mexican indigenous populations and to compare data with those reported for other native Mexican and Amerindian populations. Methods We genotyped 459 DNA samples from healthy individuals of four native Mexican populations: Yaqui, Mixteco, North Lacandon and South Lacandon for CYP2C9*2 and CYP2C9*3 alleles using a TaqMan qPCR allelic discrimination assay, and CYP2C19*2 and CYP2C19*3 alleles using polymerase chain reaction–restriction fragment length polymorphisms (PCR–RFLP). Results Frequencies were in the range 0.7–2.4% for the CYP2C9*2 allele and 0.5–7.8% for the CYP2C9*3 allele. The CYP2C19*2 allele was found in a high frequency (range, 6.0–19.3%), while CYP2C19*3 was not found. Haplotype G A CA (CYP2C19*2–CYP2C9*1), which harbours the loss-function allele CYP2C19*2, was observed in almost all populations studied, in the range 5.9–19.3%. Genetic variability was observed mainly between northern and southern populations, both among our studied populations and among other native populations of Mexico and other Amerindians (p Conclusion This study highlights the genetic variability of the Mexican native population and, because the CYP2C19*2 allele was the most frequent in almost all our studied populations, also draws attention to the potential clinical impact of this allele in vulnerable and isolated groups such as native populations of Mexico.

Background and Aims There is evidence that family history of type 2 diabetes (FHT2D) and single nucleotide polymorphisms (SNP) on the IL-6 gene promoter region are separately associated with the risk of developing type 2 diabetes. However the relationship between adult Mexican subjects with FHT2D and genotypes/haplotypes for IL-6 gene has not been explored. The aim of the present work was to study the prevalence of IL-6 −598G>A−572G>C−174G>C haplotypes among subjects with FHT2D and to determine whether their presence influences the relationship between FHT2D and risk factors for diabetes. Methods Two hundred fifty eight nondiabetic subjects participated in this study; 153 with and 105 without FHT2D. Polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) was used for genotyping. Logistic regression analysis was employed to assess the impact of IL-6 haplotypes on FHT2D per se and hyperinsulinemia and insulin resistance as risk factors for diabetes. Results Subjects with FHT2D showed a higher prevalence of hyperinsulinemia and insulin resistance (IR) than those without FHT2D (14.4 vs. 5.7%, p = 0.029, and 14.2 vs. 7.0% p = 0.050, respectively). Lower prevalence of −598 -572-174 (AGC)-haplotype (19%) in subjects with FHT2D was observed as well as a lower prevalence of hyperinsulinemia and IR among AGC haplotype carriers (12 and 14%, respectively). The relationship between FHT2D and IR was modified by the presence of AGC haplotype (from OR, 2.70; 95% CI, 0.99–7.36; p = 0.050 OR, 30.08; 95% CI, 0.58–1,568.06; p = 0.092). Conclusions IL-6 −598/−572/−174 (AGC) haplotype has a low prevalence among first-degree relatives of subjects with type 2 diabetes. Our results suggest that this haplotype is associated with decreased risk of type 2 diabetes in Mexican subjects with FHT2D.

Background Gestational diabetes mellitus (GDM) is characterized by insulin resistance. It has been described that tumor necrosis factor α (TNF-α) plays a key role in the pathogenesis of insulin resistance; moreover, increased levels of this proinflammatory cytokine have been reported in women with GDM. Therefore, this study was aimed to assess the presence of associations between the -308G/A and -238G/A polymorphisms and specific haplotypes of the TNF-α gene promoter region and insulin resistance in Mexican women with GDM. Methods This study included 51 women with GDM and 44 pregnant women with normal glucose tolerance. Measurements of anthropometric parameters and biochemical estimations were performed. We genotyped the TNF-α -308G/A and -238G/A polymorphisms using polymerase chain reaction-restriction fragment length polymorphism analysis. Results The genotype and allele frequencies of both polymorphisms did not differ significantly between the women with GDM and the controls. However, we found that the frequency of the AG haplotype was significantly increased in the patients with GDM compared with controls ( P = 0.019; odds ratio, 4.11; 95% confidence interval, 1.31-12.85). In patients with GDM, we observed that insulin levels and homeostasis model assessment of insulin resistance were significantly higher in women bearing the G/G genotype than in carriers of the G/A and A/A genotypes of the -308G/A polymorphism ( P = 0.022 and P = 0.043, respectively). Conclusions Our results suggest that the G/G genotype of the TNF-α -308G/A polymorphism increases insulin levels and insulin resistance in women with GDM and that the AG haplotype is a genetic risk factor for GDM in our study population.

Background and Aims. Interleukin-6isaninflammatoryresponsemediatorusedasametabolic marker of obesity. Polymorphisms IL6 � 597COA, � 572GOC, and � 174GOC modify the production of this protein. The associations between these haplotypes and obesity or metabolic markers have not been studied in adolescents, so an analysis of these associations was performed. Methods. The cross-sectional study included 745 apparently healthy 14- to 19-year-old adolescents. Obesity, serum glucose, insulin, triglycerides, total cholesterol, low-density lipoproteinecholesterol, high-density lipoproteinecholesterol (HDL-C), and highsensitivity C-reactive protein (hs-CRP) were evaluated, and IL6 � 597GOA, � 572GOC and � 174GOC polymorphisms determined. The associations were analyzed using multivariate logistic regression models. Results. The allele frequencies were 0.15 for � 597A and � 174C and 0.30 for � 572C. Genotypes were in HardyeWeinberg equilibrium. IL-6 � 597/� 572/� 174 haplotypes GGG, GCG, and AGC comprised 99.74% of the total haplotypes. The associations were significant between genotype GCG/GCG and hyperglycemia (OR52.86, 95% CI51.02e7.97); between GCG/GCG and high hs-CRP (OR56.17,95% CI51.13e33.77); betweenAGC/ AGC and obesity (OR 5 4.42, 95% CI 5 1.40e14.01); and between GGG/GCG and low HDL-C (OR 5 1.53, 95% CI 5 1.03e2.28). Conclusions. Genotypes of the IL6 � 597/� 572/� 174 polymorphisms are associated with metabolic risk factors in Mexican adolescents. 2013 IMSS. Published by Elsevier Inc.

The non-syndromic anterior cervical hypertrichosis (OMIM N° 600457) is a genetic disorder characterized by a patch of hair at the level of the laryngeal prominence. We present a 12-year-old boy with anterior cervical hypertrichosis and mild generalized hypertrichosis. He has no neurological, ophthalmological or skeletal anomalies. The clinical follow up is 10 years.

The Lacandones are considered descendants of the Maya Civilization that found refuge in the jungle during the Spanish colonization. They were able to live in absolute isolation until 1990 when an acculturation process began. This is a cross-sectional study that included 46.7% of the total Lacandon population. Weight, height, overnight fasting plasma glucose, urea, creatinine, uric acid, hemoglobin, triglycerides and HDL-cholesterol levels were determined. BMI and age have a positive correlation for subjects younger than 40 years (r = 0.51). Diabetes prevalence is 1.1%, and all cases are in the most acculturated town (Palenque). Prediabetes prevalence is 5.85% and all the cases have also hypertriglyceridemia. 19% of the prediabetes cases are between 10 and 19 years old. Hypercholesterolemia and hypertriglyceridemia prevalences are 20.7% and 45.1% respectively and there are cases in all the age groups. The study showed the need to implement public health programs to revert the obesity tendency in the young Lacandon population to avoid in long term the burden of non-communicable diseases that would affect most of their productive life.

The aim of this study was to investigate the association of the rs2240308 and rs1133683 polymorphisms in the AXIN2 gene with colorectal cancer (CRC) in Mexican patients.Genomic DNAs from 201 CRC patients and 100 healthy blood donors were analyzed for AXIN2 gene polymorphisms by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Statistical associations were calculated using the odds ratio (OR) test.The genotype distribution of the rs1133683 polymorphism C T showed a statistical difference between the two study groups (p = 0.0019). Moreover, OR analyses demonstrated that individuals with either the C/T or T/T genotype have a decreased risk for CRC compared with individuals with the C/C genotype (OR = 0.47, 95% confidence interval [CI] = 0.25-0.86, p = 0.0134 and OR = 0.24, 95% CI = 0.10-0.57, p = 0.005, respectively). This association was also evident in a stratified analysis based on tumor-node-metastasis (TNM) stage. For the rs2240308 polymorphism C T, the OR analysis showed a significantly increased risk for carriers of the T/T genotype (OR = 2.64, 95% CI = 1.12-6.24, p = 0.0236) and this association was also evident in the stratified analysis by TNM stage.Our results indicate the possibility that variations in the AXIN2 gene may play a significant role in promoting or preventing CRC development.

Objectives To determine whether the well-known genetic structure of the Mexican population observed with other multiallelic markers can be detected by analyzing functional polymorphisms of cytokine and other inflammatory-response-related genes. Methods A total of 834 Mestizo individuals from five Mexican cities and 92 Lacandonians – an Amerindian group from southeastern Mexico – were genotyped for 14 polymorphisms in the CRP, IL10, IL6, TGFB1, TNFA, LTA, ICAM1 IFNG, and IL1RN genes. Allele and haplotype frequencies were used for genetic structure analysis using F–statistics pairwise distances and multidimensional scaling plot. Ancestry analysis was performed, as well. Results Significant interpopulational differences at the allele and haplotype frequency level were observed, mainly between Northern (Guadalajara, Monterrey, and Culiacan) and Southern (Tierra Blanca and Puebla) Mexican populations. Also, low but significant substructure was detected between some populations from these two broad regions. Interestingly, both Lacandonian populations were highly differentiated from each other and with respect to Mestizos. Consistent with previous data, Amerindian ancestry in the Southern Mexican groups was higher compared to Northern ones. Conclusions The Mexican population exhibits regional differences in functional polymorphisms of inflammatory-response genes, as observed for other genetic markers. This information constitutes a reference for epidemiological studies that include these genetic markers to assess the susceptibility of the Mexican population to several immune-response-related diseases, such as diabetes, obesity, and renal disease, which have been shown to be common in the Mexican population but with prevalence differences within this country.

Introduction: The MDM2 gene plays an important role as negative regulator of the p53 tumor suppressor. Data on polymorphisms in the MDM2 gene have revealed associations with cancer, particularly for the rs2279744 promoter polymorphism (309 T > G), which attenuates the P53 pathway and promotes tumorigenesis in the mammary gland. Material and Methods: We examined the role of the MDM2 309 T > G polymorphism through a comparison of the genotypes of 408 healthy Mexican women with those of 529 Mexican women with breast cancer (BC). Results: The genotype frequencies of the MDM2 309 T > G polymorphism in controls and BC patients were 25% and 23% for T/T (wild type), 50% in BC and controls for T/G, and 25 and 27% for G/G (polymorphic type), respectively. The obtained odds ratio (OR) was 1.07, with a 95% confidence interval (95% CI) of 0.79-1.45, p = 0.64 for the T/GG/ G genotypes. The association was evident when the distributions of the G/G genotypes in patients exhibiting the following characteristics were compared: breastfeeding >6 months (OR 2.1, 95% CI 1.3-3.4, p = 0.002), obesity (OR 1.8, 95% CI 1.2-2.7, p = 0.003) and high GGT levels (OR 1.7, 95% CI 1.1-2.5, p = 0.012). The genotype G/G of the MDM2 309 T > G. Conclusions: The MDM2 309 T > G polymorphism was associated with BC susceptibility, particularity in breastfeeding, obesity and high GGT levels in the analyzed Mexican population.

OBJECTIVES The study's objective was to assess the association between the PRSS1 R122H and N29I and the SPINK1 N34S mutations and acute pancreatitis (AP) and recurrent pancreatitis in Mexican pediatric patients. METHODS The N34S and R122H mutations were detected using polymerase chain reaction-restriction fragment length polymorphism, and the N29I mutation was detected using allele-specific polymerase chain reaction in 92 pancreatitis patients (58 AP and 34 recurrent pancreatitis patients) and 144 controls. RESULTS We found 1 mutated allele in 4 (4.3%) of 92 pancreatitis patients and none in the controls. All 4 patients bearing mutations had AP, with a frequency of 6.8% (4/58). Three (5.2%) of 58 patients were heterozygous for the N34S mutation, and 1 (1.7%) of 58 patients was heterozygous for the N29I mutation. The comparison between the AP and control groups revealed both a significant number of patients carrying any mutations in the screened genes (P = 0.008) and bearing the N34S mutation (P = 0.023). Moreover, we found that the N34S G allele increased the risk of developing AP (odds ratio, 10.3; confidence interval, 1.1-248.8). CONCLUSIONS Patients bearing the N34S G allele exhibited a 10-fold increased risk of developing AP compared with controls, suggesting that the SPINK1 N34S mutation represents an etiologic risk factor for AP in our Mexican pediatric patients.

To identify the presence of HPV DNA in cervical as well as in placental tissue of pregnant Mexican women and to determine which type is more frequent. In a cross-sectional study, 56 placental samples were obtained from 72 pregnant women. HPV DNA was extracted and amplified with polymerase chain reaction using a consensus primer and then identified by type using RsaI endonuclease. The main outcome measures were placenta with/without HPV relation and HPV types in placenta. HPV DNA was identified in 75% of cervical tissue samples and 47.2% of placental tissue samples. Type 18 was the most frequently identified HPV type. There was a higher frequency of HPV DNA found in the cervix of Mexican women during pregnancy than reported in the previous studies. Its identification in full-term placental tissue has no relation to the type of delivery in childbirth.

Objective: We undertook this study to determine the relationship among -174G>C and 598G>A polymorphisms in the promoter region of interleukin-6, obesity, and metabolic abnormalities in subjects from central Mexico. Methods: Included in the study were 150 subjects who were not first-degree relatives of patients with diabetes and 106 blood samples from the general population. All were genotyped using polymerase chain reaction (PCR) restriction fragment-length polymorphism. Logistic regression analysis was used to assess the relationships among haplotypes, obesity, and metabolic abnormalities. Results: Only 2 haplotypes were observed: the -174G -598G and -174C -598A (D'=1.00). The -174G -598G-haplotype was associated with type 2 diabetes (OR 3.35, 95%, CI 1.16-9.71). The relationship of obesity with insulin insensitivity and obesity with hyperinsulinemia was modified by the presence of this haplotype (from OR 10.07, 95% CI 3.86-23.30 to OR 12.20, 95% CI 4.40-33.85 and OR 6.70, 95% CI 2.02-22.23 to OR 8.08, 95% CI 2.28-28.62, respectively). Conclusions: In the Mexican population, interleukin-6 haplotypes are associated with diabetes, suggesting that their contribution may be by means of modifying the relationship between obesity and metabolic abnormalities.