Distribution of CYP2D6 and CYP2C19 Polymorphisms Associated with Poor Metabolizer Phenotype in Five Amerindian Groups and Western Mestizos from Mexico

Abstract

Background: The distribution of polymorphisms in the CYP2D6 and CYP2C19 genes allows inferring the potential risk for specific adverse drug reactions and lack of therapeutic effects in humans. This variability shows differences among human populations. The aim of this study was to analyze single-nucleotide polymorphisms related to a poor metabolizer (PM) phenotype in nonpreviously studied Amerindian groups and Mestizos (general admixed population) from Mexico. Methods: We detected by SNaPshot Ò different polymorphisms located in CYP2D6 (*3, *4, *6, *7, and *8) and CYP2C19 (*2, *3, *4 and *5) in western Mestizos (n = 145) and five Amerindian groups from Mexico: Tarahumaras from the North (n = 88); Purépechas from the Center (n = 101); and Tojolabales (n = 68), Tzotziles (n = 88), and Tzeltales (n = 20) from the Southeast. Genotypes were observed by capillary electrophoresis. The genetic relationships among these populations were estimated based on these genes. Results and Discussion: The wild-type allele (*1) of both genes was predominant in the Mexican populations studied. The most widely observed alleles were CYP2C19*2 (range, 0%-31%) and CYP2D6*4 (range, 1.2%-7

CYP2C9, CYP2C19, ABCB1 genetic polymorphisms and phenytoin plasma concentrations in Mexican-Mestizo patients with epilepsy

“…[29][30][31][32] In both our patient and volunteer MM samples, we observed a predominance of the wild-type CYP2C19*1 allele, a low frequency of CYP2C19*2 and an absence of CYP2C19*3 allele, as it has been previously reported. [33][34][35][36][37][38] The frequency of CYP2C19*17 allele found in the present study (MM from Central Mexico) shows a minor nonsignificant difference from that found in a recent report in MM from the state of Jalisco (0.09 and 0.14, respectively). 38 The frequency of ABCB1 3435C4T in the MM population studied here is similar to that found in previous reports.…”

CYP2D6 Gene Polymorphisms and Predicted Phenotypes in Eight Indigenous Groups from Northwestern Mexico

“…The frequency of this allele was similar (~14%) between Mestizos from different states of Mexico and showed high variability among different indigenous groups. The Tepehuanos showed the lowest CYP2D6*4 frequency (0.385%), similar to that reported in Asians [24], and the frequency in Coras was similar to that reported in Tojolabales from Chiapas, Mexico [15].…”

“…The Guarijío group had a similar CYP2D6*4 allele frequency (3.3%) to the ones reported for Tzotziles of Chiapas, Mexico (2.7%) and Purépechas of Michoacán, Mexico (2.9%) [15] and a lower frequency than reported for Mapuches from Chile (3.6%) [25] and Tzeltales from Chiapas (5.3%) [15].…”

“…Conclusion: Our data show a lower frequency of CYP2D6 inactive alleles and a higher frequency of duplication/multiplication of CYP2D6 active alleles in indigenous populations that in Mestizos. [15]. Recently, 14 novel variants were identified in Mexican Mestizos, including CYP2D6*82, which was hypothesized to be Amerindian origin because its identification in three Mexican Amerindian groups, Mixtecos (5%), Tepehuanos (3.3%) and Mayas (1.67%) [16].…”

“…Recently, 14 novel variants were identified in Mexican Mestizos, including CYP2D6*82, which was hypothesized to be Amerindian origin because its identification in three Mexican Amerindian groups, Mixtecos (5%), Tepehuanos (3.3%) and Mayas (1.67%) [16]. A predicted CYP2D6 PM phenotype was lacking in the Mexican Amerindian population, while the frequency in Mexican Mestizos is 2-3.6% [14,15,17]. Little is known about the genetic variation of CYP2D6 in indigenous populations northernmost from Mexico, which shows larger genetic distances from the rest of the Mexican populations [18].…”