title: A novel duplication type of CYP2A6 gene in African-American population.
abstract: Human CYP2A6 is responsible for the metabolism of nicotine and its genetic polymorphisms affect smoking behavior and risk of lung cancer. In the present study, we identified a novel type of CYP2A6 gene duplication that is created through an unequal crossover event with the CYP2A7 gene at 5.2 to 5.6 kilobases downstream from the stop codon. The novel duplication type of CYP2A6 was found in African Americans (n = 176) at an allele frequency of 1.7%, but was not found in European-American (n = 187), Korean (n = 209), or Japanese (n = 184) populations. The plasma cotinine/nicotine ratio in subjects possessing the novel CYP2A6 gene duplication with the CYP2A6*1 allele (10.8 +/- 7.0, n = 4) was 1.4-fold higher than that in homozygotes of the wild type (8.0 +/- 5.0, n = 87), although the difference was not statistically significant. The findings in the present study suggested that the novel duplicated CYP2A6 allele, which is specific for African Americans, would increase nicotine metabolism and may affect smoking behavior.
authors.affiliation: Drug Metabolism and Toxicology, Division of Pharmaceutical Sciences, Graduate School of Medical Science, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan.
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Fukami
authors.forename: Miki
authors.initials: M
authors.lastname: Nakajima
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamanaka
authors.forename: Yasunari
authors.initials: Y
authors.lastname: Fukushima
authors.forename: Howard L
authors.initials: HL
authors.lastname: McLeod
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Yokoi
mesh_terms: D001741:Black or African American / Q000235:genetics*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002638:Chewing Gum; D003367:Cotinine / Q000097:blood; D003434:Crossing Over, Genetic; D065637:Cytochrome P-450 CYP2A6; D000072467:Cytochrome P450 Family 2; D005260:Female; D020440:Gene Duplication; D005787:Gene Frequency; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009538:Nicotine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000378:metabolism; D010641:Phenotype; D011109:Polymethacrylic Acids / Q000008:administration & dosage / Q000378:metabolism; D011145:Polyvinyls / Q000008:administration & dosage / Q000378:metabolism; D012907:Smoking / Q000235:genetics* / Q000378:metabolism; D061485:Tobacco Use Cessation Devices; D044465:White People / Q000235:genetics
chemical_list: D002638:Chewing Gum; D018722:Nicotinic Agonists; D011109:Polymethacrylic Acids; D011145:Polyvinyls; D009538:Nicotine; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; C423964:CYP2A7 protein, human; D065637:Cytochrome P-450 CYP2A6; D000072467:Cytochrome P450 Family 2; D003367:Cotinine