Gender-Dependent Association of FTO Polymorphisms with Body Mass Index in Mexicans.

To evaluate the associations between six single-nucleotide polymorphisms (SNPs) in intron 1 of FTO and body mass index (BMI), a case-control association study of 2314 unrelated Mexican-Mestizo adult subjects was performed. The association between each SNP and BMI was tested using logistic and linear regression adjusted for age, gender, and ancestry and assuming additive, recessive, and dominant effects of the minor allele. Association analysis after BMI stratification showed that all five FTO SNPs (rs1121980, rs17817449, rs3751812, rs9930506, and rs17817449), were significantly associated with obesity class II/III under an additive model (P<0.05). Interestingly, we also documented a genetic model-dependent influence of gender on the effect of FTO variants on increased BMI. Two SNPs were specifically associated in males under a dominant model, while the remainder were associated with females under additive and recessive models (P<0.05). The SNP rs9930506 showed the highest increased in obesity risk in females (odds ratio = 4.4). Linear regression using BMI as a continuous trait also revealed differential FTO SNP contributions. Homozygous individuals for the risk alleles of rs17817449, rs3751812, and rs9930506 were on average 2.18 kg/m(2) heavier than homozygous for the wild-type alleles; rs1121980 and rs8044769 showed significant but less-strong effects on BMI (1.54 kg/m(2) and 0.9 kg/m(2), respectively). Remarkably, rs9930506 also exhibited positive interactions with age and BMI in a gender-dependent manner. Women carrying the minor allele of this variant have a significant increase in BMI by year (0.42 kg/m(2), P = 1.17 x 10(-10)). Linear regression haplotype analysis under an additive model, confirmed that the TGTGC haplotype harboring all five minor alleles, increased the BMI of carriers by 2.36 kg/m(2) (P = 1.15 x 10(-5)). Our data suggest that FTO SNPs make differential contributions to obesity risk and support the hypothesis that gender differences in the mechanisms involving these variants may contribute to disease development

LD structure of SNPs in intron 1 of <i>FTO</i> in A) MMs and B) MAs.

<p>Black represents very high LD (r²) and white indicates a lack of correlation between SNPs. r² was calculated with Haploview 4.2.</p

Heterogenous Distribution of <i>MTHFR</i> Gene Variants among Mestizos and Diverse Amerindian Groups from Mexico

<div><p>Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate metabolism. Folate deficiency has been related to several conditions, including neural tube defects (NTDs) and cardiovascular diseases. Hence, <i>MTHFR</i> genetic variants have been studied worldwide, particularly the C677T and A1298C. We genotyped the C677T and A1298C <i>MTHFR</i> polymorphisms in Mexican Amerindians (MAs), from the largest sample included in a genetic study (n = 2026, from 62 ethnic groups), and in a geographically-matched Mexican Mestizo population (MEZ, n = 638). The 677T allele was most frequent in Mexican individuals, particularly in MAs. The frequency of this allele in both MAs and MEZs was clearly enriched in the South region of the country, followed by the Central East and South East regions. In contrast, the frequency of the 1298C risk allele in Mexicans was one of the lowest in the world. Both in MAs and MEZs the variants 677T and 1298C displayed opposite allele frequency gradients from southern to northern Mexico. Our findings suggest that in Mestizos the 677T allele was derived from Amerindians while the 1298C allele was a European contribution. Some subgroups showed an allele frequency distribution that highlighted their genetic diversity. Notably, the distribution of the frequency of the 677T allele was consistent with that of the high incidence of NTDs reported in MEZ.</p></div

Geographic distribution of allele frequencies for the C677T polymorphism in the MA population.

<p>CDMX, Mexico City; MEX, Mexico State; MOR, Morelos; OAX, Oaxaca; PUE, Puebla; SLP, San Luis Potosí. Striped States were not sampled because they are inhabited by neighboring indigenous included in this study. *States without indigenous population [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0163248#pone.0163248.ref032" target="_blank">32</a>].</p

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

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

Role of age and comorbidities in mortality of patients with infective endocarditis.

The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups: A total of 3120 patients with IE (1327  There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in th