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Drug Metabolism and Disposition Fast Forward
First published on January 31, 2007; DOI: 10.1124/dmd.106.013557

0090-9556/07/3504-515-520$20.00
DMD 35:515-520, 2007

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SHORT COMMUNICATION

A Novel Duplication Type of CYP2A6 Gene in African-American Population

Tatsuki Fukami, Miki Nakajima, Hiroyuki Yamanaka, Yasunari Fukushima, Howard L. Mcleod, and Tsuyoshi Yokoi

Drug Metabolism and Toxicology, Division of Pharmaceutical Sciences, Graduate School of Medical Science, Kanazawa University, Kakuma-machi, Kanazawa, Japan (T.F., M.N., H.Y., Y.F., T.Y.); and Department of Medicine, Washington University School of Medicine, St. Louis, Missouri (H.L.M.)

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.

Address correspondence to: Dr. Miki Nakajima, Drug Metabolism and Toxicology, Division of Pharmaceutical Sciences, Graduate School of Medical Science, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan. E-mail: nmiki{at}kenroku.kanazawa-u.ac.jp




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