Nicotine metabolism and CYP2A6 allele frequencies in Koreans
Nicotine metabolism and CYP2A6 allele frequencies in Koreans
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DOI：
10.1097/00008571-200106000-00006
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发表时间：
2001-06-01
期刊：
影响因子：
--
通讯作者：
Yokoi, T
中科院分区：
文献类型：
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作者：
Kwon, JT;Nakajima, M;Yokoi, T
CYP 2A 6是尼古丁代谢为可替宁的主要催化剂，以前，我们证明了日本人尼古丁代谢的个体间差异与CYP 2A 6基因的遗传多态性有关。为了阐明尼古丁代谢和CYP 2A 6等位基因频率的种族差异，我们研究了209名韩国人的尼古丁代谢和CYP 2A 6基因型。计算咀嚼一片尼古丁口香糖后2 h血浆浓度的可替宁/尼古丁比值，作为尼古丁代谢指标。采用聚合酶链反应（PCR）-限制性片段长度多态性或等位基因特异性（AS）-PCR检测CYP 2A 6基因（CYP 2A 6 * 1A、CYP 2A 6 *1B、CYP 2A 6 *2、CYS 2A 6 *3、CYP 2A 6 *4和CYP 2A 6 *5）的基因型。CYP 2A 6 *1A、CYP 2A 6 *2B、CYP 2A 6 *4和CYP 2A 6 *5等位基因频率在韩国人（分别为45.7%、42.8%、11.0%和0.5%）和日本人（分别为42.4%、37.5%、20.1%和0%）中存在种族差异。与日本人相似，在韩国人中未发现CYP 2A 6 *2和CYP 2A 6 *3等位基因，CYP 2A 6 *4等位基因的纯合子（4例受试者）完全缺乏可替宁形成，与日本人的数据一致。CYP 2A 6 *4杂合子代谢率较低（CYP2A6*1A/CYP2A6*4，4.79 ± 3.17; CYP2A6*1B/CYP2A6*4，7.43 ± 4.97）（CYP2A6*1A/CYP2A6*1A，7.42 ± 6.56; CYP2A6*1A/CYP2A6*1B，9.85 ± 16.12; CYP2A6*1B/CYP2A6*1B，11.33 ± 9.33）。具有CYP 2A 6 *1B等位基因的受试者似乎显示出更高的可替宁形成能力。结果表明，朝鲜族尼古丁代谢的个体间差异与CYP 2A 6基因多态性密切相关。（8.73 +/- 11.88）转移到比日本人更高的比率（3.78 ± 3.09），在每个基因型组中，韩国受试者的代谢率显著高于日本受试者，可替宁形成的种族差异可能是由于环境和/或饮食因素以及遗传因素。药理遗传学11：317-323（C）2001 Lippincott威廉姆斯和威尔金斯。
CYP2A6 is a major catalyst of nicotine metabolism to cotinine, Previously, we demonstrated that the interindividual difference in nicotine metabolism is related to a genetic polymorphism of the CYP2A6 gene in Japanese. To clarify the ethnic differences in nicotine metabolism and frequencies of CYP2A6 alleles, we studied nicotine metabolism and the CYP2A6 genotype in 209 Koreans. The cotinine/nicotine ratio of the plasma concentration 2 h after chewing one piece of nicotine gum was calculated as an index of nicotine metabolism. The genotypes of CYP2A6 gene (CYP2A6*1A, CYP2A6*1B, CYP2A6*2, CYS2A6*3, CYP2A6*4 and CYP2A6*5) were determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism or allele specific(AS)-PCR. There were ethnic differences in the allele frequencies of CYP2A6*1A, CYP2A6*2B, CYP2A6*4 and CYP2A6*5 between Koreans (45.7%, 42.8%, 11.0% and 0.5%, respectively) and Japanese (42.4%, 37.5%, 20.1% and 0%, respectively, our previous data). Similar to the Japanese, no CYP2A6*2 and CYP2A6*3 alleles were found in Koreans, The homozygotes of the CYP2A6*4 allele (four subjects) were completely deficient in cotinine formation, being consistent with the data among Japanese. The heterozygotes of CYP2A6*4 tended to possess a lower metabolic ratio (CYP2A6*1A/CYP2A6*4, 4.79 +/-3.17; CYP2A6*1B/CYP2A6*4, 7.43 +/- 4.97) than that in subjects without the allele (CYP2A6*1A/CYP2A6*1A, 7.42 +/- 6.56; CYP2A6*1A/CYP2A6*1B, 9.85 +/- 16.12; CYP2A6*1B/CYP2A6*1B, 11.33 +/- 9.33). The subjects who possess the CYP2A6*1B allele appeared to show higher capabilities of cotinine formation. It was confirmed that the interindividual difference in nicotine metabolism was closely related to the genetic polymorphism of CYP2A6, The probit plot of the metabolic ratios in Koreans (8.73 +/- 11.88) was shifted to a higher ratio than that in the Japanese (3.78 +/- 3.09), In each genotype group, the Korean subjects revealed significantly higher metabolic ratios than the Japanese subjects, The ethnic difference in cotinine formation might be due to environmental and/or diet factors as well as genetic factors. Pharmacogenetics 11:317-323 (C) 2001 Lippincott Williams & Wilkins.