title: Characterisation and PCR-based detection of a CYP2A6 gene deletion found at a high frequency in a Chinese population.
abstract: 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.
authors.affiliation: Division of Molecular Toxicology, National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Oscarson
authors.forename: R A
authors.initials: RA
authors.lastname: McLellan
authors.forename: H
authors.initials: H
authors.lastname: Gullstén
authors.forename: Q Y
authors.initials: QY
authors.lastname: Yue
authors.forename: M A
authors.initials: MA
authors.lastname: Lang
authors.forename: M L
authors.initials: ML
authors.lastname: Bernal
authors.forename: B
authors.initials: B
authors.lastname: Sinues
authors.forename: A
authors.initials: A
authors.lastname: Hirvonen
authors.forename: H
authors.initials: H
authors.lastname: Raunio
authors.forename: O
authors.initials: O
authors.lastname: Pelkonen
authors.forename: M
authors.initials: M
authors.lastname: Ingelman-Sundberg
mesh_terms: D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D065637:Cytochrome P-450 CYP2A6; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D018076:DNA, Complementary; D005387:Finland; D017353:Gene Deletion; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics*; D008969:Molecular Sequence Data; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods*
chemical_list: D018076:DNA, Complementary; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6