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首页> 外文期刊>Pharmacogenetics >Genetic polymorphism of UDP-glucuronosyltransferase 2B7 (UGT2B7) at amino acid 268: ethnic diversity of alleles and potential clinical significance.
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Genetic polymorphism of UDP-glucuronosyltransferase 2B7 (UGT2B7) at amino acid 268: ethnic diversity of alleles and potential clinical significance.

机译：UDP-葡萄糖醛酸转移酶2B7（UGT2B7）在氨基酸268的遗传多态性：等位基因的种族多样性和潜在的临床意义。

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摘要

UGT2B7 catalyses the glucuronidation of a diverse range of drugs, environmental chemicals and endogenous compounds. Hence, coding region polymorphisms of UGT2B7 are potentially of pharmacological, toxicological and physiological significance. Two variant UGT2B7 cDNAs encoding enzymes with either His or Tyr at residue 268 have been isolated. The variants, referred to as UGT2B7*1 and UGT2B7*2, respectively, arise from a C to T transversion at nucleotide 802 of the UGT2B7 coding region. Analysis of genomic DNA from 91 unrelated Caucasians and 84 unrelated Japanese demonstrated the presence of the variant alleles encoding UGT2B7*1 and UGT2B7*2 in both populations. However, while there was an approximately equal distribution of subjects homozygous for each allele in the Caucasian population, subjects homozygous for the UGT2B7*1 allele were over 10-fold more prevalent than UGT2B7*2 homozygotes in Japanese. The frequencies of the UGT2B7*1 and UGT2B7*2 alleles were 0.511 and 0.489, respectively, in Caucasians, and 0.732 and 0.268, respectively, in Japanese. The 95% confidence intervals for the two alleles did not overlap between Caucasians and Japanese. Rates of microsomal androsterone, menthol and morphine (3-position) glucuronidation were determined for genotyped livers from Caucasian donors. Statistically significant inter-genotypic differences were not apparent for any of the three substrates. Although the UGT2B7 polymorphism characterized here is probably not associated with altered enzyme activity, the results highlight the need to consider ethnic variability in assessing the consequences of UGT polymorphisms.
机译：UGT2B7催化各种药物，环境化学物质和内源性化合物的葡萄糖醛酸苷化。因此，UGT2B7的编码区多态性可能具有药理，毒理和生理学意义。已经分离出编码在残基268具有His或Tyr的酶的两个变体UGT2B7 cDNA。分别称为UGT2B7 * 1和UGT2B7 * 2的变体来自UGT2B7编码区核苷酸802处的C到T转换。对来自91位无关的白种人和84位无关的日本人的基因组DNA的分析表明，两种人群中均存在编码UGT2B7 * 1和UGT2B7 * 2的变异等位基因。但是，尽管白种人群体中每个等位基因纯合子的受试者分布大致相等，但在日本，UGT2B7 * 1等位基因纯合子的流行率比UGT2B7 * 2纯合子高10倍以上。 UGT2B7 * 1和UGT2B7 * 2等位基因的频率在白种人中分别为0.511和0.489，在日语中分别为0.732和0.268。两个等位基因的95％置信区间在高加索人和日本人之间没有重叠。确定了来自白种人供体的基因型肝的微粒体雄激素，薄荷醇和吗啡（3位）葡萄糖醛酸化率。对于这三种底物中的任何一种，统计上的显着基因型间差异均不明显。尽管此处表征的UGT2B7多态性可能与酶活性的改变不相关，但结果强调了在评估UGT多态性的后果时需要考虑种族差异。

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