Genetic variability among Mexican Mestizo and Amerindian populations based on three ABCB1 polymorphisms.

The most widely studied polymorphisms of the ABCB1 gene are rs1128503 (c.1236C>T), rs2032582 (c.2677G>T/A), and rs1045642 (c.3435C>T). Although variation in ABCB1 allele frequencies among Mexican Mestizos (admixed) from different regions has been observed, Mexican Amerindians have been poorly studied. We aimed to describe the genetic variability of these three ABCB1 polymorphisms in a total sample of 273 Mexican volunteers that included Mestizos from the state of Yucatán, and Amerindians from seven populations (Tarahumara, Mayo, Huichol, Purépecha, Nahua, Tojolabal, and Maya). Genotypes were determined by means of Taq Man probes (qPCR). Genotype distribution was in Hardy-Weinberg equilibrium for all three ABCB1polymorphisms in the eight Mexican populations analyzed. For c.1236C>T and c.3435C>T, the heterozygous C/T was the most frequent genotype in the majority of the studied Mexican populations (range 30.8-65.4%), while heterozygous G/T was the most common genotype for c.2677G>T/A (range 25.9-51.2%), mainly followed by G/G (range 3.2-47.1%) and T/T (range 7.0-35.5%). 12 haplotypes were estimated from the three ABCB1 polymorphisms analyzed, with TTT the most frequent haplotype (mean, 37.0%). Genetic differentiation was demonstrated among the studied Mexican populations (Fst p value < 0.0001), which could imply a diverse drug response or a risk for adverse drug reactions to ABCB1 substrates. Although differences among Amerindians are probably due to genetic drift effects, for Mestizos this could imply variation in admixture composition. In conclusion, interpopulation variability in the observed frequencies of ABCB1 polymorphisms among Mexican Mestizos and Amerindians allow predicting diverse drug responses to ABCB1 substrates in these populations.