Relevance of CYP2D6 Gene Variants in Population Genetic Differentiation

Abstract

A significant portion of the variability in complex features, such as drug response, is likely caused by human genetic diversity. One of the highly polymorphic pharmacogenes is CYP2D6, encoding an enzyme involved in the metabolism of about 25% of commonly prescribed drugs. In a directed search of the 1000 Genomes Phase III variation data, 86 single nucleotide polymorphisms (SNPs) in the CYP2D6 gene were extracted from the genotypes of 2504 individuals from 26 populations, and then used to reconstruct haplotypes. Analyses were performed using Haploview, Phase, and Arlequin softwares. Haplotype and nucleotide diversity were high in all populations, but highest in populations of African ancestry. Pairwise FST showed significant results for eleven SNPs, six of which were characteristic of African populations, while four SNPs were most common in East Asian populations. A principal component analysis of CYP2D6 haplotypes showed that African populations form one cluster, Asian populations form another cluster with East and South Asian populations separated, while European populations form the third cluster. Linkage disequilibrium showed that all African populations have three or more haplotype blocks within the CYP2D6 gene, while other world populations have one, except for Chinese Dai and Punjabi in Pakistan populations, which have two.

CYP2D6 and CYP2C19 Variant Coverage of Commercial Antidepressant Pharmacogenomic Testing Panels Available in Victoria, Australia

“…Over 15% of Victoria's population are of Chinese, Indian, Vietnamese, Sri Lankan, Filipino, Māori, Samoan, or Korean ancestry, and 6.5% are Aboriginal and/or Torres Strait Islanders, the Indigenous people of Australia. Immigration to Australia from Africa has increased over the past decade [27], which may increase allelic variation, given that African populations have the highest CYP2D6 haplotype diversity [28]. Despite an ethnically diverse population, there is limited published information about allelic diversity at CYP2C19 and CYP2D6 in Australia.…”

Exploring CYP2D6 polymorphisms and angiotensin receptor blocker response in the Bai hypertensive population

“…This unique domain structure enables the enzyme to oxidize a wide range of pharmaceutical compounds. Responsible for metabolizing nearly a quarter of all clinically used drugs, including adrenergic antagonists [ 7 , 8 ] and ARBs [ 9 ], CYP2D6 exhibits considerable polymorphic diversity. To date, over 172 CYP2D6 gene variants have been identified ( https://www.pharmvar.org/ , last accessed: 11 December 2023), with many of which are linked to reduced enzymatic function, potentially affecting drug efficacy [ 10 , 11 ].…”