Association of Nuclear Factor-Erythroid 2-Related Factor 2, Thioredoxin Interacting Protein, and Heme Oxygenase-1 Gene Polymorphisms with Diabetes and Obesity in Mexican Patients

The nuclear factor-erythroid 2- (NF-E2-) related factor 2 (Nrf2) is abated and its ability to reduce oxidative stress is impaired in type 2 diabetes and obesity. Thus, the aim of this study was to explore if polymorphisms in Nrf2 and target genes are associated with diabetes and obesity in Mexican mestizo subjects. The rs1800566 of NAD(P)H:quinone oxidoreductase 1 (NQO1) gene, rs7211 of thioredoxin interacting protein (TXNIP) gene, rs2071749 of heme oxygenase-1 (HMOX1) gene, and the rs6721961 and the rs2364723 from Nrf2 gene were genotyped in 627 diabetic subjects and 1020 controls. The results showed that the rs7211 polymorphism is a protective factor against obesity in nondiabetic subjects (CC + CT versus TT, OR = 0.40, P=0.005) and in women (CC versus CT + TT, OR = 0.7, P=0.016). TT carriers had lower high-density lipoprotein cholesterol levels and lower body mass index. The rs2071749 was positively associated with obesity (AA versus AG + GG, OR = 1.25, P=0.026). Finally, the rs6721961 was negatively associated with diabetes in men (CC versus CA + AA, OR = 0.62, P=0.003). AA carriers showed lower glucose concentrations. No association was found for rs1800566 and rs2364723 polymorphisms. In conclusion, the presence of Nrf2 and related genes polymorphisms are associated with diabetes and obesity in Mexican patients

Dyslipidemia, Obesity, and Ethnicity in Mexican Children

The aim of this study was to assess lipid disorders in children from five ethnic groups, both urban and indigenous, from northern and central Mexico. We measured the lipid profile to determine the ability of the body mass index (BMI) to discriminate an abnormally high lipid level using receiving operating characteristics (ROC). We analyzed the association and interaction of obesity and ethnicity with lipid disorders using generalized linear models in 977 children. The highest prevalence of lipid disorders (high TG, high TC, high LDL, high APOB, and dyslipidemia) was found in central Mexico-Mexico City and urban northern Mexico. The BMI performed better at predicting low HDL in Seris, a northern indigenous group (0.95, CI: 0.69–0.85), and Mexico City (0.75, CI: 0.69–0.82), and high LDL in Puebla (central Mexico, 0.80, CI: 0.69–0.85). Obesity significantly (p < 0.05) increases lipid disorders by around two times (OR~2) for almost all lipid markers. Obesity and ethnic interaction increase the lipid disorders by more than five times for different lipid markers and ethnic groups (high total cholesterol OR = 5.31; low HDL OR = 5.11, and dyslipidemia OR = 5.68). Lipid disorders are not restricted to children with high BMIs, but obesity exacerbates these. The emerging lipid disorder risk depends on the ethnic group

Association of the PSRC1 rs599839 Variant with Coronary Artery Disease in a Mexican Population

Background and Objectives: Coronary artery disease (CAD) is a major health problem in México. The identification of modifiable risk factors and genetic biomarkers is crucial for an integrative and personalized CAD risk evaluation. In this work, we aimed to validate in a Mexican population a set of eight selected polymorphisms previously associated with CAD, myocardial infarction (MI), or dyslipidemia. Materials and Methods: A sample of 907 subjects (394 CAD cases and 513 controls) 40–80 years old was genotyped for eight loci: PSRC1 (rs599839), MRAS (rs9818870), BTN2A1 (rs6929846), MTHFD1L (rs6922269), CDKN2B (rs1333049), KIAA1462 (rs3739998), CXCL12 (rs501120), and HNF1A (rs2259816). The association between single nucleotide polymorphisms (SNPs) and CAD was evaluated by logistic regression models. Results: Multiple logistic regression analysis with adjustment by age, gender, and body mass index showed that rs599839 was significantly associated with CAD (ORADD = 0.72, p = 0.009; ORDOM = 0.66, p = 0.007). Conclusions: The PSRC1 rs599839 polymorphism shows a significant protective association with CAD in this sample of the Mexican population

Genome-Wide Association Study of Body Mass Index and Body Fat in Mexican-Mestizo Children

Background: Childhood obesity is a major health problem in Mexico. Obesity prevalence estimated by body mass index (BMI) is almost half than that estimated by percent body fat (%BF) in the Childhood Obesity pediatric cohort (COIPIS). Objective. We performed a genome-wide association study (GWAS) of BMI and %BF in 828 children from the COIPIS to identify markers of predisposition to high values for both phenotypes used for obesity classification. Methods: For the GWAS we used the LAT Axiom 1, Affymetrix and 2.5 million single loci from the 1000 Genomes Phase 3 imputation panel. We used a linear model, adjusted by age, sex, and Amerindian ancestry assuming an additive inheritance model. Results. Genome-wide significance (p ≤ 5.0 × 10−8) and 80% of statistical power was reached for associations of two loci in two genes (CERS3 and CYP2E1) to BMI. Also, 11 loci in six genes (ANKS1B, ARNTL2, KCNS3, LMNB1, SRGAP3, TRPC7) reached genome-wide significance for associations to %BF, though not 80% of statistical power. Discussion: None of the SNPs were previously reported as being associated to BMI or %BF. In addition, different loci were found for BMI and %BF. These results highlight the importance of gaining deeper understanding of genetic markers of predisposition to high values for the phenotypes used for obesity diagnosis

Common Polymorphisms Linked to Obesity and Cardiovascular Disease in Europeans and Asians are Associated with Type 2 Diabetes in Mexican Mestizos

Background and objectives: Type 2 diabetes (T2D) is a major problem of public health in Mexico. We investigated the influence of five polymorphisms, previously associated with obesity and cardiovascular disease in Europeans and Asians, on T2D in Mexican Mestizos. Materials and Methods: A total of 1358 subjects from 30 to 85 years old were genotyped for five loci: CXCL12 rs501120; CDNK2A/B rs1333049; HNF-1α rs2259816; FTO rs9939609; and LEP rs7799039. We used logistic regressions to test the effect of each locus on T2D in two case⁻control groups with obesity and without obesity. Also, linear regression models on glucose and glycated hemoglobin (HbA1c) were carried out on the whole sample, adjusted by age, gender, and body mass index. Results: The CXCL12 rs501120 C allele (OR = 1.96, p = 0.02), the FTO rs9939609 A allele (OR = 2.20, p = 0.04) and the LEP rs7799039 A allele (OR = 0.6, p = 0.03) were significantly associated with T2D in obesity case⁻control group. No significant association was found in the non-obesity case⁻control group. The linear regression model showed that CDNK2A/B rs1333049 C allele (β = 0.4, p = 0.03) and FTO rs9939609 A allele (β = 0.5, p = 0.03), were significantly associated with HbA1c, but no association was found among the loci with the glucose levels. Conclusions: Polymorphisms previously linked with obesity and cardiovascular events were also associated with T2D and high levels of HbA1c. Furthermore, we must point at the fact that this is the first report where polymorphisms CXCL12 rs501120 and LEP rs7799039 are associated with T2D in subjects with obesity

Family Functioning and Suicide Attempts in Mexican Adolescents

Suicide is considered a public health problem that affects families worldwide. Family functioning is the capability of the family system to fulfill needs during the stages of its development. In this study, we focused on evaluating family cohesion and adaptability in a group of adolescents who had attempted suicide and were hospitalized at a hospital for mental health disorders, compared to a control group. Methods: based on Olson’s circumplex model, we used the FACES III scale to gain insights into the family functioning of both suicidal and control groups. Results: The case group presented lower scores in cohesion and adaptability compared to the control group, with moderate effect-size for cohesion (Cohen’s d/r test = 1.217/0.52) and low effect-size for adaptability (Cohen’s d/r test = 0.746/0.35) (p < 0.001 for both variables), and also presented predominantly disengaged families (72.5% in the case group vs. 27.5% in the control group) and structured families (45% in the case group vs. 23.8% in the control group). The type of family described by the adolescents with a history of suicide attempts may explain the presence of low self-esteem and little emotional support usually present in this type of patient

Family Functioning and Suicide Attempts in Mexican Adolescents

Suicide is considered a public health problem that affects families worldwide. Family functioning is the capability of the family system to fulfill needs during the stages of its development. In this study, we focused on evaluating family cohesion and adaptability in a group of adolescents who had attempted suicide and were hospitalized at a hospital for mental health disorders, compared to a control group. Methods: based on Olson’s circumplex model, we used the FACES III scale to gain insights into the family functioning of both suicidal and control groups. Results: The case group presented lower scores in cohesion and adaptability compared to the control group, with moderate effect-size for cohesion (Cohen’s d/r test = 1.217/0.52) and low effect-size for adaptability (Cohen’s d/r test = 0.746/0.35) (p < 0.001 for both variables), and also presented predominantly disengaged families (72.5% in the case group vs. 27.5% in the control group) and structured families (45% in the case group vs. 23.8% in the control group). The type of family described by the adolescents with a history of suicide attempts may explain the presence of low self-esteem and little emotional support usually present in this type of patient

Interaction between FTO rs9939609 and the Native American-origin ABCA1 rs9282541 affects BMI in the admixed Mexican population

Abstract Background The aim of this study was to explore whether interactions between FTO rs9939609 and ABCA1 rs9282541 affect BMI and waist circumference (WC), and could explain previously reported population differences in FTO-obesity and FTO-BMI associations in the Mexican and European populations. Methods A total of 3938 adults and 636 school-aged children from Central Mexico were genotyped for both polymorphisms. Subcutaneous and visceral adipose tissue biopsies from 22 class III obesity patients were analyzed for FTO and ABCA1 mRNA expression. Generalized linear models were used to test for associations and gene-gene interactions affecting BMI, WC and FTO expression. Results FTO and ABCA1 risk alleles were not individually associated with higher BMI or WC. However, in the absence of the ABCA1 risk allele, the FTO risk variant was significantly associated with higher BMI (P = 0.043) and marginally associated with higher WC (P = 0.067), as reported in Europeans. The gene-gene interaction affecting BMI and WC was statistically significant only in adults. FTO mRNA expression in subcutaneous abdominal adipose tissue according to ABCA1 genotype was consistent with these findings. Conclusions This is the first report showing evidence of FTO and ABCA1 gene variant interactions affecting BMI, which may explain previously reported population differences. Further studies are needed to confirm this interaction