CYP2D6 in Amerindians from Southern Mexico: low variability and higher frequency of functional alleles

Abstract

Several functional and nonfunctional CYP2D6 variants have been associated with interindividual and interethnic variability in pharmacological responses. The aim of this article was to study the diversity and the interpopulation relationships of CYP2D6 variants of south Native Mexicans to define predicted phenotypes. A fully systematic review of CYP2D6 variants reported in Amerindian populations before 2015 was performed (NCBI, Google Scholar, and 1000 Genomes Project databases). Allele data were analyzed by methods such as heat map, dissimilarity matrix, dendogram, and principal component analysis using complete-linkage clustering method. Five original studies on CYP2D6 covering 13 Native Mexican populations were identified; three of these described CYP2D6 allele frequencies were in south Native Mexican populations. Overall, CYP2D6 allele variability is scarce in southern Native Mexican populations: besides the functional alleles *1 and *2 and the null variant *4, the other variants have frequencies <0.05. This implies that most of the southern Native Mexican populations may be considered CYP2D6 extended metabolizers. The statistical analyses tend to cluster the native communities by their geographical origin, but in a disperse pattern suggesting distinct subpopulation structures. CYP2D6 functional variants are prevalent in Native Mexicans, and they may be predicted as extended drug metabolizers. In addition, allele frequencies are related to the geographic distribution of the Amerindian groups and display important population stratification.