纯合子CYP2A6缺失对尼古丁代谢的意义：一种使用单重PCR-RFLP的CYP2A6基因分型新方法。

The significance of the homozygous CYP2A6 deletion on nicotine metabolism: a new genotyping method of CYP2A6 using a single PCR-RFLP.

作者信息

Kitagawa K, Kunugita N, Katoh T, Yang M, Kawamoto T

机构信息

Department of Environmental Health, School of Health Science, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.

出版信息

Biochem Biophys Res Commun. 1999 Aug 19;262(1):146-51. doi: 10.1006/bbrc.1999.1182.

DOI:10.1006/bbrc.1999.1182

PMID:10448083

Abstract

A convenient and specific CYP2A6 genotyping method was developed in this study. This method consisting of a single PCR-RFLP is capable of resolving the genotype into either CYP2A61 (wild type), CYP2A62, or CYP2A63. Among 252 Japanese persons genotyped, 241 were genotyped as the wild type, 1 as an unknown variant, and none as either CYP2A62 or CYP2A6*3. A homozygous deletion was found in the 10 remaining subjects. To clarify the metabolic significance of this deletion in the whole human body, urinary cotinine, the principal metabolite of nicotine, was analyzed subsequent to smoking. Cumulated urinary cotinine excretion in the homozygously CYP2A6-deleted individuals was about one-seventh compared to the control group (wild type). This study provides a firm experimental basis for correlating genotypic characterization of CYP2A6 with phenotypic expression of nicotine metabolism.

摘要

本研究开发了一种简便且特异的CYP2A6基因分型方法。这种由单一PCR-RFLP组成的方法能够将基因型解析为CYP2A61（野生型）、CYP2A62或CYP2A63。在252名进行基因分型的日本人中，241人被基因分型为野生型，1人为未知变异型，无人为CYP2A62或CYP2A6*3。在其余10名受试者中发现了纯合缺失。为阐明这种缺失在整个人体中的代谢意义，在吸烟后分析了尼古丁的主要代谢产物尿可替宁。与对照组（野生型）相比，CYP2A6纯合缺失个体的累积尿可替宁排泄量约为七分之一。本研究为将CYP2A6的基因特征与尼古丁代谢的表型表达相关联提供了坚实的实验基础。