Genetic variations of the SLCO1B1 gene in the Chinese, Malay and Indian populations of Singapore.
OATP1B1 is a liver-specific transporter that mediates the uptake of various endogenous and exogenous compounds including many clinically used drugs from blood into hepatocytes. This study aims to identify genetic variations of SLCO1B1 gene in three distinct ethnic groups of the Singaporean population (n=288). The coding region of the gene encoding the transporter protein was screened for genetic variations in the study population by denaturing high-performance liquid chromatography and DNA sequencing. Twenty-five genetic variations of SLCO1B1, including 10 novel ones, were found: 13 in the coding exons (9 nonsynonymous and 4 synonymous variations), 6 in the introns, and 6 in the 3' untranslated region. Four novel nonsynonymous variations: 633A>G (Ile211Met), 875C>T (Ala292Val), 1837T>C (Cys613Arg), and 1877T>A (Leu626Stop) were detected as heterozygotes. Among the novel nonsynonymous variations, 633A>G, 1837T>C, and 1877T>A were predicted to be functionally significant. These data would provide fundamental and useful information for pharmacogenetic studies on drugs that are substrates of OATP1B1 in Asians.
Ho
Woon Fei
WF
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore.
Koo
Seok Hwee
SH
Yee
Jie Yin
JY
Lee
Edmund Jon Deoon
EJ
D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics*; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D007194:India / Q000453:epidemiology / Q000208:ethnology; D027381:Liver-Specific Organic Anion Transporter 1; D008296:Malaysia / Q000453:epidemiology / Q000208:ethnology; D008297:Male; D008875:Middle Aged; D027361:Organic Anion Transporters / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D012846:Singapore / Q000453:epidemiology / Q000208:ethnology; D055815:Young Adult
D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; C503999:SLCO1B1 protein, human