A novel duplication type of CYP2A6 gene in African-American population
A novel duplication type of CYP2A6 gene in African-American population
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DOI：
10.1124/dmd.106.013557
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发表时间：
2007-04-01
影响因子：
3.9
通讯作者：
Yokoi, Tsuyoshi
中科院分区：
文献类型：
--
作者：
Fukami, Tatsuki;Nakajima, Miki;Yokoi, Tsuyoshi
人类CYP2A6负责尼古丁的代谢，其基因多态性影响吸烟行为和肺癌的风险。在目前的研究中，我们发现了一种新型的CYP2A6基因重复，它是通过与CYP2A7基因在停止密码子下游5.2至5.6千碱基处的不平等交叉事件产生的。在非裔美国人（n = 176）中发现了新的CYP2A6重复型，等位基因频率为1.7%，但在欧美人（n = 187）、韩国人（n = 209）和日本人（n = 184）人群中未发现。具有CYP2A6*1等位基因的新型CYP2A6基因重复者血浆可替宁/尼古丁比值（10.8 +/- 7.0,n = 4）比野生型纯合子（8.0 +/- 5.0,n = 87）高1.4倍，但差异无统计学意义。本研究结果表明，非裔美国人特有的新型重复CYP2A6等位基因会增加尼古丁代谢，并可能影响吸烟行为。
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.