CYP2A7多态性等位基因干扰了CYP2A6*4A等位基因的基因分型。

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

作者信息

Fukami T, Nakajima M, Sakai H, McLeod H L, Yokoi T

机构信息

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

出版信息

Pharmacogenomics J. 2006 Nov-Dec;6(6):401-12. doi: 10.1038/sj.tpj.6500390. Epub 2006 Apr 25.

DOI:10.1038/sj.tpj.6500390

PMID:16636685

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 CYP2A64A allele (entire CYP2A6 gene deleted allele). From the subjects, we found CYP2A7 polymorphic alleles (CYP2A71B, CYP2A71C, and CYP2A71D) in which the sequences in the 3'-flanking region were converted to the corresponding CYP2A6 sequences, being confused with the CYP2A64A. 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 CYP2A64A 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.

摘要

人类细胞色素P450（CYP）2A6可将尼古丁代谢为可替宁。CYP2A6的基因多态性导致了尼古丁代谢的个体间差异。我们遇到了一些虽然被基因分型为CYP2A64A等位基因（整个CYP2A6基因缺失等位基因）杂合子，但却拥有两份CYP2A6基因拷贝的受试者。从这些受试者中，我们发现了CYP2A7多态性等位基因（CYP2A71B、CYP2A71C和CYP2A71D），其3'侧翼区域的序列被转换为相应的CYP2A6序列，与CYP2A64A混淆。这些等位基因在欧裔美国人（n = 187）中的频率分别为1.3%、2.1%、0.3%，但在非裔美国人（n = 176）、日本人（n = 184）和韩国人（n = 209）中非常罕见。通过一种改进的基因分型方法，欧裔美国人中CYP2A64A的等位基因频率从3.7%被校正为0%。本研究中开发的这种易于理解且可靠的基因分型方法将有助于评估基因型与表型之间的关联。