Unraveling Signatures of Local Adaptation among Indigenous Groups from Mexico.

Few studies have addressed how selective pressures have shaped the genetic structure of the current Native American populations, and they have mostly limited their inferences to admixed Latin American populations. Here, we searched for local adaptation signals, based on integrated haplotype scores and population branch statistics, in 325 Mexican Indigenous individuals with at least 99% Native American ancestry from five previously defined geographical regions. Although each region exhibited its own local adaptation profile, only PPARG and AJAP1, both negative regulators of the Wnt/ß catenin signaling pathway, showed significant adaptation signals in all the tested regions. Several signals were found, mainly in the genes related to the metabolic processes and immune response. A pathway enrichment analysis revealed the overrepresentation of selected genes related to several biological phenotypes/conditions, such as the immune response and metabolic pathways, in agreement with previous studies, suggesting that immunological and metabolic pressures are major drivers of human adaptation. Genes related to the gut microbiome measurements were overrepresented in all the regions, highlighting the importance of studying how humans have coevolved with the microbial communities that colonize them. Our results provide a further explanation of the human evolutionary history in response to environmental pressures in this region.

The genomic landscape of Mexican Indigenous populations brings insights into the peopling of the Americas.

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.

Association of the -629C>A (rs1800775) CETP Polymorphism with the Development of Essential Hypertension in Mexican Population.

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 extensively explored. We evaluated four polymorphisms of the CEPT gene -827C>T, -631C>A, -630C>A, and -629C>A in patients with essential hypertension (EH). Materials and Methods: A total of 160 hypertensive (HT) patients and 160 normotensive (NT) individuals were studied. Blood pressure was measured and blood samples were collected for biochemical anlayses and DNA extraction. Polymorphisms were identified using Sanger sequencing. Genotype, genotype combination, allele, and haplotype frequencies were analyzed. Associations between the SNPs and EH were explored using multiple linear regression models. Results: Under the dominant model, the -629A allele reduced the odds of having EH (odds ratio [OR] = 0.58, 95% confidence interval [CI], 0.34-0.98; p = 0.04), whereas the genotype combination -631CC/-629CC increased the risk of HT (OR = 2.21, 95% CI, 1.23-3.95, p = 0.008). In HT patients, the -629A allele was associated with increased insulin levels (ß = 4.0, 95% CI, 1.21-6.68, p = 0.005), and homeostatic model assessment of insulin resistance (ß = 0.9, 95% CI, 0.17-1.72, p = 0.018), and in NT individuals it was associated with increased high-density lipoprotein cholesterol levels (ß = 3.0, 95% CI, 0.20-5.78, p = 0.036). Conclusion: The CETP -629A allele reduces the odds of having essential arterial hypertension in the Mexican population. Moreover, it exerts a variable effect on diverse biomarkers analyzed in both NT and HT groups.

Association analysis of calpain 10 gene variants/haplotypes with gestational diabetes mellitus among Mexican women.

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.

Analysis of cytokine gene polymorphisms in Mestizo and native populations from Mexico.

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.

CYP2C9 and CYP2C19 Allele and Haplotype Distributions in Four Mestizo Populations from Western Mexico: An Interethnic Comparative Study.

AIMS: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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.

[Association analysis of SNP-63 and indel-19 variant in the calpain-10 gene with polycystic ovary syndrome in women of reproductive age]. / Análisis de asociación del SNP-63 y la variante indel-19 del gen de calpaína-10 con síndrome de ovario poliquístico en mujeres en edad reproductiva.

BACKGROUND: Polycystic ovary syndrome is a complex and heterogeneous disease involving both reproductive and metabolic problems. It has been suggested a genetic predisposition in the etiology of this 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 relation with the polycystic ovary syndrome, because this syndrome is associated with hyperinsulinemia 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 variant indel-19 of the 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 significatly between women with polycystic ovary syndrome and 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 (p = 0.8353). CONCLUSIONS: The results suggest that SNP-63 and indel-19 variant of the CAPN10 gene do not represent a risk factor for polycystic ovary syndrome in our patients group.

Glutathione peroxidase 3 serum levels and GPX3 gene polymorphisms in subjects with metabolic syndrome.

BACKGROUND AND AIMS: Glutathione peroxidase 3 (GPx3) plays a main role in removing hydro- and lipoperoxides from the body. Changes in concentration and several single-nucleotide polymorphisms (SNP) at the GPX3 gene have been associated with vascular diseases, but the relationship of GPx3 with metabolic syndrome (MetS) remains unexplored. We undertook this study to determine the association of GPx3 serum levels and several GPX3 SNPs with the presence of MetS in Mexican subjects. METHODS: Clinical, biochemical, and anthropometric evaluation were conducted in 426 subjects assigned to three groups: control (n = 42); risk group (RG, n = 200), and MetS group (n = 184). Insulin sensitivity (IS) and cardiovascular risk were determined by the QUICKI and TG/HDL-C index, respectively. Serum GPx3 was determined by enzyme immunoassay and polymorphisms within GPX3 gene were identified by nucleotide sequencing. RESULTS: MetS group showed low IS and increased cardiovascular risk with respect to controls as well as higher GPx3 serum levels (172.9 ± 32.2 vs. 145.6 ± 24.8 ng/dL; p <0.05). Only three of the ten GPX3 SNPs screened were polymorphic with two haplotypes observed (CCT and TTA-rs8177404, rs8177406, and rs8177409), indicating tight linkage disequilibrium in this genetic region. No differences for either genotype or allele frequencies among groups were observed, but rs8177409 (allele T) was associated with cardiovascular risk (odds ratio [OR], 4.5; p = 0.0125). CONCLUSION: This study shows that serum levels of GPx3 are increased in subjects with MetS and that rs8177409 SNP was associated with cardiovascular risk in a Mexican population.

Low prevalence of interleukin-6 haplotypes associated with a decreased risk of type 2 diabetes in Mexican subjects with a family history of type 2 diabetes.

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.

[Pharmacogenetics and antiepileptic drug metabolism: implication of genetic variants in cytochromes P450]. / Farmacogenetica y metabolismo de farmacos antiepilepticos: implicacion de variantes geneticas en citocromos P450.

INTRODUCTION: Antiepileptic drugs (AEDs) are used for the seizures control in patients with epilepsy, however 20-30% of epileptic patients are drug resistant. Several factors contributing to the variability of the AEDs response, and this variability can be partially attributed to the presence of sequence variations (polymorphisms) in genes encoding enzymes involved in the AEDs metabolism. AIM: To describe the polymorphisms in genes that encoding for proteins involved in the metabolism of some of the major AEDs, focusing on enzymes cytochrome P450 (CYP450). DEVELOPMENT: There are some polymorphisms in genes encoding proteins involved in drug metabolism, particularly enzymes of superfamily CYP450, that are already considered of clinical utility in the therapeutic management. These genetic variants contribute to the variability of the activity of metabolizing enzymes, which in turn influencing the poor or inadequate therapeutic response, as well as in the occurrence of adverse effects. CONCLUSIONS: The identification of interindividual variability in the response to AEDs may allow the personalized treatment with the aim of maximize the efficiency and minimize risk, regardless of the clinical variability and adverse effects could be manifest in a minority of the patients.

TITLE: Farmacogenetica y metabolismo de farmacos antiepilepticos: implicacion de variantes geneticas en citocromos P450.Introduccion. Los farmacos antiepilepticos (FAE) son la base para el control de las crisis en pacientes con epilepsia; sin embargo, se conoce que el 20-30% de los pacientes son farmacorresistentes. Son diversos los factores que contribuyen a la variabilidad de la respuesta a los FAE, y esta variabilidad puede atribuirse, al menos en parte, a la presencia de polimorfismos (variaciones de la secuencia) en genes que codifican para enzimas involucradas en el metabolismo de los FAE. Objetivo. Describir las variaciones de la secuencia en genes que codifican para proteinas implicadas en el metabolismo de algunos de los principales FAE, con enfasis en las enzimas citocromo P450 (CYP450). Desarrollo. Existen algunos polimorfismos en genes que codifican para proteinas involucradas en el metabolismo de farmacos, particularmente enzimas de la superfamilia CYP450, que se consideran ya de utilidad clinica en el manejo terapeutico. La presencia de estas variantes geneticas contribuye a la variabilidad de la actividad de enzimas metabolizadoras, lo que, a su vez, influye en la pobre o inadecuada respuesta terapeutica, e incluso en la aparicion de efectos adversos. Conclusiones. La identificacion de la variabilidad interindividual en la respuesta a los diversos FAE puede permitir la individualizacion del tratamiento con la intencion de maximizar su eficacia y minimizar el riesgo, independientemente de que la variabilidad clinica y los efectos adversos se presenten en una minoria de pacientes.

Farmacogenética y metabolismo de fármacos antiepilépticos: implicación de variantes genéticas en citocromos P450 / Pharmacogenetics and antiepileptic drug metabolism: implication of genetic variants in cytochromes P450

Introducción. Los fármacos antiepilépticos (FAE) son la base para el control de las crisis en pacientes con epilepsia; sin embargo, se conoce que el 20-30% de los pacientes son farmacorresistentes. Son diversos los factores que contribuyen a la variabilidad de la respuesta a los FAE, y esta variabilidad puede atribuirse, al menos en parte, a la presencia de polimorfismos (variaciones de la secuencia) en genes que codifican para enzimas involucradas en el metabolismo de los FAE. Objetivo. Describir las variaciones de la secuencia en genes que codifican para proteínas implicadas en el metabolismo de algunos de los principales FAE, con énfasis en las enzimas citocromo P450 (CYP450). Desarrollo. Existen algunos polimorfismos en genes que codifican para proteínas involucradas en el metabolismo de fármacos, particularmente enzimas de la superfamilia CYP450, que se consideran ya de utilidad clínica en el manejo terapéutico. La presencia de estas variantes genéticas contribuye a la variabilidad de la actividad de enzimas metabolizadoras, lo que, a su vez, influye en la pobre o inadecuada respuesta terapéutica, e incluso en la aparición de efectos adversos. Conclusiones. La identificación de la variabilidad interindividual en la respuesta a los diversos FAE puede permitir la individualización del tratamiento con la intención de maximizar su eficacia y minimizar el riesgo, independientemente de que la variabilidad clínica y los efectos adversos se presenten en una minoría de pacientes (AU

Introduction. Antiepileptic drugs (AEDs) are used for the seizures control in patients with epilepsy, however 20-30% of epileptic patients are drug resistant. Several factors contributing to the variability of the AEDs response, and this variability can be partially attributed to the presence of sequence variations (polymorphisms) in genes encoding enzymes involved in the AEDs metabolism. Aim. To describe the polymorphisms in genes that encoding for proteins involved in the metabolism of some of the major AEDs, focusing on enzymes cytochrome P450 (CYP450). Development. There are some polymorphisms in genes encoding proteins involved in drug metabolism, particularly enzymes of superfamily CYP450, that are already considered of clinical utility in the therapeutic management. These genetic variants contribute to the variability of the activity of metabolizing enzymes, which in turn influencing the poor or inadequate therapeutic response, as well as in the occurrence of adverse effects. Conclusions. The identification of interindividual variability in the response to AEDs may allow the personalized treatment with the aim of maximize the efficiency and minimize risk, regardless of the clinical variability and adverse effects could be manifest in a minority of the patients (AU)

Association analysis between -308G/A and -238G/A TNF-alpha gene promoter polymorphisms and insulin resistance in Mexican women with gestational diabetes mellitus.

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.

Serum levels of glutathione peroxidase 3 in overweight and obese subjects from central Mexico.

BACKGROUND AND AIMS: Overweight and obesity are considered complex entities in which there are alterations in the concentration of antioxidant enzymes. It has been reported that glutathione peroxidase 3 (GPx3), an extracellular enzyme involved in the reduction of both hydro- and lipoperoxides, shows changes both in gene expression and protein concentration in animal models for type 2 diabetes (T2D) and obesity, but the variability of GPx3 levels in different human populations and under different health conditions are currently unclear. We undertook this study to determine the GPx3 levels in overweight and obese subjects from central Mexico. METHODS: Biochemical profile (serum glucose, insulin and lipid profile) and GPx3 concentrations were determined in 28 healthy subjects (control) and 133 subjects who were overweight or obese (OW-OB). RESULTS: The OW-OB group had a higher concentration of triacylglycerides (TAG) compared with the control group (201.2 ± 88.7 vs. 100.3 ± 46.4 mg/dL, p <0.05) and the TAG/high density lipoprotein-cholesterol (HDL-C) index (5.6 ± 2.8 vs. 2.1 ± 1.2, p <0.05), whereas the concentration of HDL-C decreased (38.2 ± 8.7 vs. 50.1 ± 14.5 mg/dL, p <0.05). Serum GPx3 was significantly higher in the OW-OB group than in the control group (175.4 ± 25.4 vs. 143.5 ± 23.1 ng/dL). GPx3 concentration correlated with insulin sensitivity (IS) and the TAG/HDL-C index (Rho = -0.2336 and Rho = 0.2275) (p <0.01). CONCLUSIONS: The TAG/HDL-C index and serum GPx3 concentration increased in the OW-OB group. In addition, GPx3 had a significant correlation with IS, weight, and the TAG/HDL-C index.

Screening of R122H and N29I mutations in the PRSS1 gene and N34S mutation in the SPINK1 gene in Mexican pediatric patients with acute and recurrent pancreatitis.

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.

Tumor necrosis factor-alpha gene promoter -308G/A and -238G/A polymorphisms in Mexican patients with type 2 diabetes mellitus.

The association between some Tumor necrosis factor-alpha (TNF-α) promoter polymorphisms and Type 2 diabetes mellitus (T2DM) remains controversial. Ethnic differences may play a role in these conflicting results. The aim of this study was to investigate the association between -308G/A and -238G/A polymorphisms located in the promoter region of the TNF-α gene and T2DM in Mexican mestizo patients. Nine hundred four individuals (259 patients with T2DM and 645~controls) were genotyped for the -308G/A and -238G/A polymorphisms by PCR--RFLP. We found that the -238A allele increased the risk of developing T2DM in Mexican patients (OR=1.57, 95% CI: 1.07-2.29; p=0.018). Moreover, we found that the frequency of the GA haplotype (created by the -308G and -238A alleles) was significantly increased in patients with T2DM when compared with controls (OR =1.56, 95% CI: 1.05-2.31; p=0.026). Our results suggest that the -238G/A polymorphism and a specific haplotype (GA) are genetic risk factors for the development of T2DM in Mexican population.

Influence of CRP, IL6, and TNFA gene polymorphisms on circulating levels of C-reactive protein in Mexican adolescents.

BACKGROUND AND AIMS: Obesity correlates with a chronic and low-grade inflammation status. C-reactive protein (CRP) measurement has been used as an independent risk marker for future cardiovascular events. CRP level shows interindividual variability due to environmental and genetic factors. The aim of this study was to assess the association of functional polymorphisms on CRP, IL6, and TNFA genes with serum CRP levels in Mexican mestizo adolescents. METHODS: Body mass index (BMI), serum high-sensitivity C-reactive protein (hsCRP) levels, and genotypes for CRP+1444C>T, IL6-174G>C, and TNFA-308G>A polymorphisms were obtained from 418 unrelated Mexican adolescents. Genetic association with hsCRP levels was evaluated by means of a dominant genetic model with uni- and multivariate analysis. RESULTS: Genotype frequencies for all three polymorphisms were according to Hardy-Weinberg equilibrium (HWE). CRP+1444T, TNFA-308A, and IL6-174C allele frequencies were 37, 7, and 10%, respectively. CRP+1444T was associated with higher mean CRP levels independent of age, gender and BMI (ß = 0.21; 95% confidence interval [95% CI] = 0.02-0.39); p = 0.030). IL6-174C was associated with low CRP levels in the overweight group (p = 0.005). IL6-174G>C and TNFA-308G>A allele frequencies observed from this Mexican sample were similar to data for other Mexican populations. CONCLUSIONS: The CRP+1444C>T polymorphism was associated with CRP levels in Mexican adolescents and could be used as a genetic marker for the early detection of individuals at risk for developing obesity-related conditions such as cardiovascular disease or type 2 diabetes mellitus in early adulthood.

Analysis of the association of preeclampsia with polymorphisms of the INS, INSR and IRS1 genes in Mexican women.

BACKGROUND/AIMS: It has been proposed that preeclampsia is a metabolic syndrome of pregnancy. The polymorphisms PstI and MaeIII of INS, NsiI of INSR and Ala513Pro and Gly972Arg of IRS1 have been associated with metabolic syndrome; moreover, the products of these genes are functionally contiguous during insulin signaling. The aim of this study was to assess whether these polymorphisms are associated with preeclampsia. METHODS: 46 normotensive pregnant women and 43 preeclamptic patients were included in the study to develop a clinical, biochemical and genotypic profile of preeclampsia. Clinical evaluation consisted of measurement of blood pressure, height and weight. Peripheral blood samples were collected for determination of fasting glucose and insulin concentrations and for extraction of genomic DNA. Proteinuria was determined. Polymorphisms were detected using PCR-RFLP. RESULTS: The normotensive and preeclampsia groups did not differ significantly in clinical and biochemical traits, except for systolic and diastolic blood pressure (p < 0.0001). Polymorphisms previously associated with metabolic syndrome in Mexican populations were not associated with preeclampsia in Mexican women (p > 0.05). CONCLUSION: The lack of an association between preeclampsia and the polymorphisms studied suggests that other genes whose products do not have direct functional interaction with metabolic syndrome or epigenetic factors may play a role in preeclampsia.

Congo red effect on cyst viability and cell wall structure of encysting entamoeba invadens

Background. The cell wall of Entamoeba invadens cysts is composed of chitin microfibrils as the main structural component. It has been demonstrated in yeast that the chitin cell wall assembly is altered by dyes such as Congo red (CR) and Calcofluor. Methods. The purpose of this work was to study the cell wall assambly under the effect of CR dye on encysting E. invadens by means of light and electron microscopy, after the ammebas were subjected to the effect of 100-2,000 µg CR/mL. Experiments were performed either in BI-S-33 or in mLG media. Results. Trophozoit growth was not inhibited by 100-1,000 µg/mL CR after 8 days of incubation in BI-S-33 medium. However, low levels of growth were observed with 2,000 µg/mL of dye. No significant differences in morphologically viable (hyaline) cyst production occurred after 24-48 hm when 100 µg CR/mL was used, while the highest concentration of CR (2,000 µg/mL) resulted in a significant decrease of hyaline cyst yield; dead cysts prevailed in cultures, particularly at 72 h of CR treatment. Differentiation of amebas incubated in the presence of 500-2,000 µg/mL CR produced abnormal chitin deposits, rendering irregulary thick or double cell walls, as shown by transmission and scanning electron microscopy. Cyst cultures obtained under 100 µg/mL CR produced as many trophozoites as did the control when they were incubated in BI-S-33, but only low numbers of trophozoites were found in culture cysts obtained under higher CR doses. Conclusion. Our results suggest that CR affects E. invadens encystment, alters the cell wall formation, and also affects the cyst viability