Genetic Analysis of the CYP2D6 Locus in a Hong Kong Chinese Population

Abstract

Background: The cytochrome P450 CYP2D6 enzyme debrisoquine 4-hydroxylase metabolizes many different classes of commonly used drugs, such as tricyclic antidepressants and neuroleptics. Genetic polymorphism of the CYP2D6 gene is responsible for pronounced interindividual and interracial differences in the metabolism of these drugs. The CYP2D6*10 allele and its variants are the most frequent alleles found in Orientals, and they are responsible for diminished debrisoquine 4-hydroxylase activity because of the presence of a C188→T mutation in exon 1. Methods: One hundred nineteen Hong Kong Chinese subjects were genotyped by means of allele-specific PCR, PCR, and restriction enzyme analysis for 10 CYP2D6 alleles (CYP2D6*1, *2, *4D, *5, *8/*14, *10A, *10B, *15, *16, and J9). Results: CYP2D6*10B was the most prevalent allele, and CYP2D6*10/CYP2D6*10 was the most frequent genotype, representing 46.22% of the population. Conclusions: There was no significant difference in the prevalence of the alleles analyzed between our study and the Chinese populations genotyped previously. This is the largest study in terms of the number of CYP2D6 alleles analyzed in an Oriental population and the first one conducted in a Hong Kong Chinese population.

β1-Adrenergic receptor polymorphisms influence the response to metoprolol monotherapy in patients with essential hypertension

“…To exclude the potential effect of different metoprolol concentrations among groups on the blood pressure response to metoprolol, 61 patients were genotyped for CYP2D6*10 variance, which is the most common genetic polymorphism occurring on CYP2D6 and has been confirmed to have a good correlation with metoprolol concentration in the Chinese population. 26 Other genetic polymorphisms were extremely rare in the Chinese population and were not found in these 61 patients. In fact, as shown in Tables I and II, CYP2D6 polymorphisms were equally distributed among the cohorts, which suggested that the different blood pressure response to metoprolol therapy among groups was not confounded by metoprolol plasma levels.…”

“…The genotype assay of CYP2D6*10 was performed as described previously with minor modification. 26 We used the sense primer P1 (5Ј-CCA TTT GGT AGT GAG GCA GGT AT-3Ј) and the antisense primer P2 (5Ј-CAC CAT CCA TGT TTG CTT CTG GT-3Ј) to amplify DNA fragments including CYP2D6*10. The amplified DNA fragments were digested with Hph I (TaKaRa Biotech).…”

Genetic polymorphism of CYP2D6 in Chinese subjects in Malaysia

“…None of the Chinese in the study had a genotype that predicted a PM status and the null allele (CYP2D6*4) responsible for this trait, whereas among Caucasians it occured in only one heterozygous individual. In Asia, PM occurred in 0-1% of the populations (11)(12)(13)(14)(15)(16), because of the rarity of this CYP2D6*4 allele (15,17). CYP2D6*4 was absent in Hong Kong Chinese (17) and in Singaporean Chinese (18).…”

CYP2D6 phenotypes among Malays in Malaysia

“…Within the EM phenotype, the distribution of debrisoquine MR among Chinese is shifted to the right, indicating lower enzyme activity (4,7,14). Thus, while most Swedes were found to have debrisoquine MRs of less than 1, the opposite was found for Chinese subjects (7).…”

“…Our results, although again using a small sample size, taken together with Lee's and Zahurin's, may be seen as suggesting that Malays may indeed differ from Chinese and other ethnic Asians in relation to CYP2D6 polymorphism. PM frequencies among ethnic Asians are usually less than 1% (4,5).…”