CYP2A7 polymorphic alleles confound the genotyping of CYP2A6*4A allele

The Pharmacogenomics Journal
Tatsuki FukamiT Yokoi

Abstract

Human cytochrome P450 (CYP) 2A6 metabolizes nicotine to cotinine. Genetic polymorphisms of CYP2A6 contribute to the interindividual variability of nicotine metabolism. We encountered some subjects possessing two copies of the CYP2A6 gene, although they were genotyped as heterozygotes of the CYP2A6*4A allele (entire CYP2A6 gene deleted allele). From the subjects, we found CYP2A7 polymorphic alleles (CYP2A7*1B, CYP2A7*1C, and CYP2A7*1D) in which the sequences in the 3'-flanking region were converted to the corresponding CYP2A6 sequences, being confused with the CYP2A6*4A. These allele frequencies in European-Americans (n=187) were 1.3, 2.1, 0.3%, respectively, but these were very rare in African-Americans (n=176), Japanese (n=184), and Koreans (n=209). By an improved genotyping method, the allele frequency of CYP2A6*4A of 3.7% in European-Americans was corrected to 0%. The comprehensible and reliable genotyping method developed in this study would be useful to evaluate associations between the genotype and phenotype.

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Citations

Aug 14, 2008·Pharmacogenetics and Genomics·Takuro EndoYasunori Momose
Sep 17, 2008·Pharmacogenetics and Genomics·Tatsuki FukamiTsuyoshi Yokoi
Nov 21, 2008·Pharmacogenomics·Ana RossiniLuis Felipe Ribeiro Pinto
Dec 14, 2011·Annals of Behavioral Medicine : a Publication of the Society of Behavioral Medicine·Tao LiuWei-Qing Chen
Jan 5, 2016·Biological & Pharmaceutical Bulletin·Masaki KumondaiMasahiro Hiratsuka
May 25, 2007·Clinical Pharmacology and Therapeutics·J C MwenifumboR F Tyndale
Feb 18, 2014·British Journal of Pharmacology·Stephen P H AlexanderUNKNOWN CGTP Collaborators
Feb 25, 2015·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Masataka NakanoMiki Nakajima
Feb 3, 2007·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Tatsuki FukamiTsuyoshi Yokoi

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