Dataset Information

Heterogenous Distribution of MTHFR Gene Variants among Mestizos and Diverse Amerindian Groups from Mexico.

ABSTRACT: 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, MTHFR genetic variants have been studied worldwide, particularly the C677T and A1298C. We genotyped the C677T and A1298C MTHFR 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.

SUBMITTER: Contreras-Cubas C

PROVIDER: S-EPMC5029802 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Heterogenous Distribution of MTHFR Gene Variants among Mestizos and Diverse Amerindian Groups from Mexico.

Contreras-Cubas Cecilia C Sánchez-Hernández Beatríz E BE García-Ortiz Humberto H Martínez-Hernández Angélica A Barajas-Olmos Francisco F Cid Miguel M Mendoza-Caamal Elvia C EC Centeno-Cruz Federico F Ortiz-Cruz Gabriela G Jiménez-López José Concepción JC Córdova Emilio J EJ Salas-Bautista Eva Gabriela EG Saldaña-Alvarez Yolanda Y Fernández-López Juan Carlos JC Mutchinick Osvaldo M OM Orozco Lorena L Orozco Lorena L

PloS one 20160920 9

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, MTHFR genetic variants have been studied worldwide, particularly the C677T and A1298C. We genotyped the C677T and A1298C MTHFR polymorphisms in Mexican Amerindians (MAs), from the largest sample included in a genetic study (n = 2026, from 62 ethnic groups), and in a geographically-match ...[more]

PMID: 27649570

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Project description:CYP3A5 metabolizes endogenous substrates and ~30% of prescription drugs. The CYP3A5 gene contains an active CYP3A5*1 allele, and a non-functional version, the CYP3A5*3 (rs776746), with consequences for drug therapeutic responses and side effects. Both CYP3A5*1 and *3 have been associated with hypertension. The frequency of CYP3A5*3 varies between populations of different ancestries, with Europeans having the highest allele frequency (> 90%). Given the importance of CYP3A5*3 in drug response and hypertension development, the aim of the present study was to evaluate the frequency of this polymorphism and its association with hypertension in vulnerable indigenous populations in Mexico. A total of 372 subjects were recruited from eight ethnic groups in Northwest Mexico. Systolic (SBP), diastolic (DBP), and median (MBP) blood pressures as well as body mass index (BMI) were measured. Ancestry was evaluated through STR analysis, and the CYP3A5*1/*3 polymorphisms were identified using real-time PCR with TaqMan® probes. Higher frequencies of CYP3A5*1 and *3 were observed in groups with higher (>90%) and lower (<90%) Amerindian ancestry, respectively. The CYP3A5*3/*3 genotype was more frequent in indigenous women with higher SBP and DBP values. On the other hand, the *1 allele showed a protective effect against both high SBP (OR, 0.38; 95% CI, 0.17-0.83, p = 0.001) and DBP (OR 0.38, 95% CI 0.18-0.81, p = 0.007) in women. This association remained significant after adjusting for BMI and age for diastolic (OR, 0.38; 95% CI, 0.17-0.84, p = 0.011) and systolic BP (OR, 0.33; 95% CI, 0.15-0.76, p = 0.005) BP levels in women. Thus, the frequency of CYP3A5*3 varies between groups and seems to depend on ancestry, and CYP3A5*1 decreases the risk of hypertension in Mexican indigenous women. This population analysis of CYP3A5*1/*3 has profound implications not only for the susceptibility to diseases, such as hypertension, but also for safer drug administration regimens, assuring better therapeutic responses and fewer side effects.

Dataset Information

Heterogenous Distribution of MTHFR Gene Variants among Mestizos and Diverse Amerindian Groups from Mexico.

Publications

Heterogenous Distribution of MTHFR Gene Variants among Mestizos and Diverse Amerindian Groups from Mexico.

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