RT Journal Article
SR Electronic
T1 A Novel Duplication Type of <em>CYP2A6</em> Gene in African-American Population
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 515
OP 520
DO 10.1124/dmd.106.013557
VO 35
IS 4
A1 Fukami, Tatsuki
A1 Nakajima, Miki
A1 Yamanaka, Hiroyuki
A1 Fukushima, Yasunari
A1 Mcleod, Howard L.
A1 Yokoi, Tsuyoshi
YR 2007
UL http://dmd.aspetjournals.org/content/35/4/515.abstract
AB 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. The American Society for Pharmacology and Experimental Therapeutics