High frequency of CYP2D6 ultrarapid metabolizer genotypes in an Ashkenazi Jewish population from Argentina

Abstract

A twofold higher frequency of CYP2D6 ultrarapid metabolizers (estimated from genotype: gUMs) was reported among Ashkenazi Jews (AJ) living in New York (USA) than in other North American Caucasians, which might be important to guide the prescription for CYP2D6 substrates in AJ communities around the world. This study was aimed to determine whether the high frequency of CYP2D6 gUMs described in AJ from USA was replicated in AJ from Argentina when compared with other multiethnic admixture Argentines (GA). The frequency of the most common allelic variants and of CYP2D6 gUMs (>2 active genes) and poor metabolizers (0 active genes, gPMs) was also compared among the studied Argentine populations. CYP2D6 genotyping was performed in 173 AJ and 246 GA DNA samples of unrelated donors from the metropolitan area of Buenos Aires. CYP2D6 alleles (*2, *3, *4, *5, *6, *10, *17, *35, *41 and multiple copies), genotypes and functional phenotype frequencies were determined. The frequencies of gUMs and gPMs in AJ from Argentina were 11.5% and 5.2%, respectively, whereas in GA, the frequencies of gUM and gPMs were 6.5% and 4.9%, respectively. Comparisons between AJ and GA showed that gUMs frequencies were twofold higher (P<0.05) in AJ than GA. CYP2D6*35 allele was more frequent in GA than AJ, whereas CYP2D6*41 and *1xN were more frequent in AJ than in GA (P<0.05). This study supports the previously reported high frequency of gUMs on another Ashkenazi population in New York. The present findings also support the interethnic variability of CYP2D6 genetic polymorphism in the overall Argentine population.

Genomic Ancestry,CYP2D6,CYP2C9, andCYP2C19Among Latin Americans

“…In particular, the Ashkenazi Jews from Argentina show the highest frequency of CYP2D6*41 in Ibero-America (16.2%, Table S2, Figure 2b). 16 Differently, the frequencies of the decreased-activity alleles CYP2D6*17 and *29 (ranges in Ibero-America: 0-18% and 0-11%, respectively) are positively correlated and well predicted by African ancestry (R 2 > 0.88; Figure 2c,d).…”

Relevance of CYP2D6 Gene Variants in Population Genetic Differentiation

“…The genomic diversity of modern populations reflects former demographic and evolutionary changes. In isolated populations with minimal gene exchange, genetic distinctiveness is especially evident (e.g., Jewish populations, Saami, Roma, Basque), which can also be seen in pharmacogene research [60][61][62][63][64][65][66].…”