Influence of Genetic Admixture Components on Allele-Associated Hypertension in Amerindian Populations From Northwest Mexico.

metabolizes endogenous substrates and ~30% of prescription drugs. The gene contains an active allele, and a non-functional version, the (rs776746), with consequences for drug therapeutic responses and side effects. Both and have been associated with hypertension. The frequency of varies between populations of different ancestries, with Europeans having the highest allele frequency (> 90%). Given the importance of 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 polymorphisms were identified using real-time PCR with TaqMan® probes. Higher frequencies of and were observed in groups with higher (>90%) and lower (<90%) Amerindian ancestry, respectively. The / genotype was more frequent in indigenous women with higher SBP and DBP values. On the other hand, the * allele showed a protective effect against both high SBP (OR, 0.38; 95% CI, 0.17-0.83, = 0.001) and DBP (OR 0.38, 95% CI 0.18-0.81, = 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, = 0.011) and systolic BP (OR, 0.33; 95% CI, 0.15-0.76, = 0.005) BP levels in women. Thus, the frequency of varies between groups and seems to depend on ancestry, and decreases the risk of hypertension in Mexican indigenous women. This population analysis of 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.