Haplotype structure and allele frequencies of CYP2B6 in a Korean population
Haplotype structure and allele frequencies of CYP2B6 in a Korean population
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DOI：
10.1124/dmd.104.001107
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发表时间：
2004-12-01
影响因子：
3.9
通讯作者：
Jang, IJ
中科院分区：
文献类型：
--
作者：
Cho, JY;Lim, HS;Jang, IJ
细胞色素P450 2B 6（CYP 2B 6）代谢许多治疗药物，其代谢活性在人体肝脏中变化显著。虽然CYP 2B 6基因多态性在非编码区和编码区已被报道，但关于亚洲人非编码区单核苷酸多态性（SNP）及其单倍型的信息很少。14个以前报道的SNP的确定聚合酶链反应-限制性片段长度多态性或SNaPshot分析在韩国人口和他们的单倍型推断基因型数据使用期望最大化算法。最常见的单倍型是单倍型I，参考序列（频率0.35），单倍型II（0.19），单倍型III（0.19）和单倍型V（0.12），它们共占所有单倍型的85%。在白种人中，单倍型III（包含-2320 C、-1778 G、-1186 G、-750 C和15582 T）的频率比 * 1 J等位基因高2.4倍，单倍型V（包含-8207 C、-1456 C、-750 C、516 T和785 G）的频率比 * 1 J等位基因高2.4倍。是白种人 * 6 B等位基因的55%。此外，单倍型V，* 6 B等位基因，似乎是完全连锁的-8207在一个假定的核受体结合基序，这表明较低的表达 * 6 B等位基因可能与非编码SNP的存在，如-8207 G>C连接到非同义SNP。总之，我们发现了11个以前描述的多态性，并确定了四个主要的单倍型的CYP 2B 6在韩国人。* 1 J或 * 6 B等位基因的频率，这可能会降低CYP 2B 6酶的表达，被发现在韩国人和高加索人之间有显着差异。
Cytochrome P450 2B6 (CYP2B6) metabolizes a number of therapeutic drugs and its metabolic activity varies markedly in human liver. Although genetic polymorphisms of CYP2B6 have been reported in noncoding and coding regions, little information is available regarding single nucleotide polymorphisms (SNPs) and their haplotypes in noncoding regions in Asians. Fourteen previously reported SNPs were determined by polymerase chain reaction-restriction fragment length polymorphism or SNaPshot analysis in a Korean population and their haplotypes were inferred from genotype data using an expectation-maximization algorithm. The most common haplotypes were haplotype I, the reference sequence (frequency 0.35), haplotype II (0.19), haplotype III (0.19), and haplotype V (0.12), which together accounted for 85% of all haplotypes. The frequency of haplotype III, which contains -2320C, -1778G, -1186G, -750C, and 15582T, was found to be 2.4-fold higher than that of the *1J allele in Caucasians, and the frequency of haplotype V, which contains -8207C, -1456C, -750C, 516T, and 785G, was 55% of that of the *6B allele in Caucasians. Moreover, haplotype V, the *6B allele, appeared to be completely linked to -8207 within a putative nuclear receptor binding motif, suggesting that lower expressions of the *6B allele may be associated with the presence of noncoding SNPs such as -8207G>C linked to nonsynonymous SNPs. In conclusion, we found 11 previously described polymorphisms and identified four major haplotypes of CYP2B6 in Koreans. The frequencies of the *1J or *6B alleles, which may reduce CYP2B6 enzyme expression, were found to be significantly different between Koreans and Caucasians.