A novel polymorphism of human CYP2A6 gene CTP2A6*17 has an amino acid substitution (V365M) that decreases enzymatic activity in vitro and in vivo
A novel polymorphism of human CYP2A6 gene CTP2A6*17 has an amino acid substitution (V365M) that decreases enzymatic activity in vitro and in vivo
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DOI：
10.1016/j.clpt.2004.08.014
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发表时间：
2004-12-01
影响因子：
6.7
通讯作者：
Yokoi, T
中科院分区：
文献类型：
--
作者：
Fukami, T;Nakajima, M;Yokoi, T
Cytochrome P450 (CYP) 2A6 is a major CYP responsible for the metabolism of nicotine and coumarin in humans. We identified a novel allele, designated CYP2A6*17, which contains A51G (exon 1), C209T (intron 1), G1779A (exon 3), C4489T (intron 6), G5065A (V365M, exon 7), G5163A (intron 7), C5717T (exon 8), and A5825G (intron 8). We developed a genotyping method by polymerase chain reaction-restriction fragment length polymorphism for the CYP2A6*17 allele, targeting the G5065A mutation. The allele frequency in black subjects (n = 96) was 9.4% (95% confidence interval [CI], 5.3%-13.5%). The allele was not found in white subjects (95% CI, 0%-0.9%; n = 163), Japanese subjects (95% CI, 0%-1.6%; n = 92), and Korean subjects (95% CI, 0%-0.7%; n = 209). To examine the effects of the amino acid change in the CYP2A6*17 allele on the enzymatic activity, we expressed a wild-type or variant (V365M) CYP2A6 together with NADPH-CYP reductase in Escherichia coli. For coumarin 7-hydroxylation, the apparent Michaelis-Menten constant value of variant CYP2A6 (1.06 +/- 0.11 mumol/L) was significantly (P
