日本人群中编码人类胆盐输出泵（BSEP）的ABC转运蛋白基因ABCB11的遗传变异。

Genetic variations of the ABC transporter gene ABCB11 encoding the human bile salt export pump (BSEP) in a Japanese population.

作者信息

Kim Su-Ryang, Saito Yoshiro, Itoda Masaya, Maekawa Keiko, Kawamoto Manabu, Kamatani Naoyuki, Ozawa Shogo, Sawada Jun-ichi

机构信息

Project Team for Pharmacogenetics, National Institute of Health Sciences, Tokyo, Japan.

出版信息

Drug Metab Pharmacokinet. 2009;24(3):277-81. doi: 10.2133/dmpk.24.277.

DOI:10.2133/dmpk.24.277

PMID:19571440

Abstract

The bile salt export pump (BSEP) encoded by ABCB11 is located in the canalicular membrane of hepatocytes and mediates the secretion of numerous conjugated bile salts into the bile canaliculus. In this study, 28 ABCB11 exons (including non-coding exon 1) and their flanking introns were comprehensively screened for genetic variations in 120 Japanese subjects. Fifty-nine genetic variations, including 19 novel ones, were found: 14 in the coding exons (6 nonsynonymous and 8 synonymous variations), 4 in the 3'-UTR, and 41 in the introns. Three novel nonsynonymous variations, 361C>A (Gln121Lys), 667C>T (Arg223Cys), and 1460G>T (Arg487Leu), were found as heterozygotes and at 0.004 allele frequencies. These data provide fundamental and useful information for genotyping ABCB11 in the Japanese and probably other Asian populations.

摘要

由ABCB11编码的胆盐输出泵（BSEP）位于肝细胞的胆小管膜上，介导多种结合胆盐分泌到胆小管中。在本研究中，对120名日本受试者的28个ABCB11外显子（包括非编码外显子1）及其侧翼内含子进行了全面的基因变异筛查。发现了59种基因变异，包括19种新变异：14种在编码外显子中（6种非同义变异和8种同义变异），4种在3'-UTR中，41种在内含子中。发现三种新的非同义变异361C>A（Gln121Lys）、667C>T（Arg223Cys）和1460G>T（Arg487Leu）为杂合子，等位基因频率为0.004。这些数据为日本及其他亚洲人群中ABCB11的基因分型提供了基础且有用的信息。