Genetic analysis of CYP2D6 locus of Hong Kong Chinese psychiatric patients

Abstract

The genetically determined polymorphism of debrisoquine hydroxylase (cytochrome P4502D6, CYP2D6) shows marked interethnic differences due to the different distribution of the alleles of the CYP2D6 gene in different populations. Differences are not only in the incidence of poor metabolizers (PM) of debrisoquone, but also in the enzyme activity within the extensive metabolizer (EM) phenotype. The distribution of the debrisoquine metabolic ratios (MR) is shifted towards higher values among Oriental EMs compared to Caucasian EMs due to the high prevalence of the CYP2D6*10 allele [nomenclature according to Daly et al., 1996] in this population [Wang et al., 1993]. The prevalence of the different alleles of the CYP2D6 gene may be different within different Oriental populations or in particular patient groups. The genotype of 54 patients with diagnosis of major depression according to DSM IV was assessed for the prevalence of the alleles CYP2D6*10, CYP2D6*4, and CYP2D6*8 (the prevalence of which in Chinese is not known). Mutation 2938C→T indicative of CYP2D6*2 (allele L) was also assessed in five patients homozygous for CYP2D6*10 and was found to be absent. Genotyping was performed according to published methods. The CYP2D6*8 and CYP2D6*4 alleles were absent in the present population studied as expected. The CYP2D6*10 allele frequency was 0.6 in the present study, similar to that found among Singaporean Chinese, higher than that found among the Japanese, Koreans, and Chinese living in Sweden (0.51), and lower than that among Taiwanese (0.7) [Wang et al., 1993; Yokota et al., 1993; Lee and Jeyaseelan, 1994; Roh et al., 1996]. Genotyping a healthy Hong Kong Chinese population and testing for other variants of the CYP2D6 gene is in progress. This is the first CYP2D6 genotyping study conducted on a Hong Kong Chinese population. It will contribute to previous data on differences among EMs of different Oriental origins.