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

FEBS Letters

Gullstén, Harriet¹  Sinues, Blanca³  Ingelman-Sundberg, Magnus²  Lang, Matti A⁵  Raunio, Hannu¹  Hirvonen, Ari⁴  McLellan, Roman A²  Pelkonen, Olavi¹  Yue, Qun-Ying⁶  Luisa Bernal, Maria³  Oscarson, Mikael² 

[1] Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland;Division of Molecular Toxicology, National Institute of Environmental Medicine, Karolinska Institutet, Box 210, S-171 77, Stockholm, Sweden;Department of Pharmacology and Physiology, University of Zaragoza, Zaragoza, Spain;Finnish Institute of Occupational Health, Department of Industrial Hygiene and Toxicology, Helsinki, Finland;Division of Biochemistry, Faculty of Pharmacy, University of Uppsala, Uppsala, Sweden;Medical Products Agency, Uppsala, Sweden

关键词: Cytochrome P450;    Coumarin;    Gene deletion;    Unequal crossover;    Genotype;    Phenotype;    CYP or P450;    cytochrome P450;    PM;    poor metaboliser;    PCR;    polymerase chain reaction;   

DOI  :  10.1016/S0014-5793(99)00359-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Cytochrome P450 2A6 is an important human hepatic P450 which activates pre-carcinogens, oxidises some drugs and constitutes the major nicotine C-oxidase. In fact, results have been presented in the literature which suggested a relationship between the distribution of defective CYP2A6 alleles and smoking behaviour as well as cigarette consumption. In the present report, we describe the structure of a novel CYP2A locus where the whole CYP2A6 gene has been deleted, resulting in an abolished cytochrome P450 2A6-dependent metabolism. The origin of this locus is apparently due to an unequal crossover event between the 3′-flanking region of the CYP2A6 and CYP2A7 genes. A rapid PCR-based method for the detection of the CYP2A6del allele was developed 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 population, we did not detect any CYP2A6*2 alleles using an improved genotyping procedure, in contrast to the 11–20% previously reported. It is concluded that genotyping for the CYP2A6del allele is of great importance in studies correlating, for example, smoking behaviour, pre-carcinogen activation or drug metabolism to the CYP2A6 genotype, in particular when oriental populations are investigated.

【 授权许可】

Unknown