Characterisation and PCR-based detection of a CYP2A6 gene deletion found at a high frequency in a Chinese population

Cytochrome P450 2A6 is an important human hepatic P450 which activates pre- carcinogens, oxidises some drugs and constitutes the major nicotine C-oxida se, In fact, results have been presented in the literature which suggested a relationship between the distribution of defective CYP2A6 alleles and smo king behaviour as well as cigarette consumption. In the present report, we describe the structure of a novel CYP2A locus where the whole CYP2A6 gene h as been deleted, resulting in an abolished cytochrome P450 2A6-dependent me tabolism. The origin of this locus is apparently due to an unequal crossove r event between the 3'-flanking region of the CYP2A6 and CYP2A7 genes, A ra pid PCR-based method for the detection of the CYP2A6del allele was develope d and the allele frequency was 15.1% among 96 Chinese subjects, but only 1. 0% in Finns (n=100) and 0.5% in Spaniards (n=100), In the Chinese populatio n, we did not detect any CYP2A6*2 alleles using an improved genotyping proc edure, in contrast to the 11-20% previously reported. It is concluded that genotyping for the CYP2A6del allele is of great importance in studies corre lating, for example, smoking behaviour, pre-carcinogen activation or drug m etabolism to the CYP2A6 genotype, in particular when oriental populations a re investigated. (C) 1999 Federation of European Biochemical Societies.