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Pharmacogenomics J. 2006 Nov-Dec;6(6):401-12. Epub 2006 Apr 25.

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

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  • 1Department of Drug Metabolism and Toxicology, Division of Pharmaceutical Sciences, Graduate School of Medical Science, Kanazawa University, Kakuma-machi, Kanazawa, Japan.


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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