期刊
DRUG METABOLISM AND PHARMACOKINETICS
卷 23, 期 6, 页码 476-482出版社
JAPANESE SOC STUDY XENOBIOTICS
DOI: 10.2133/dmpk.23.476
关键词
SLCO1B1; pharmacogenetics; human genetics; single nucleotide polymorphism; clinical pharmacology
资金
- Agency for Science, Technology and Research, Biomedical Research Council, Singapore [BMRC/01/1/21/17/054]
- National Medical Research Council, Ministry of Health, Singapore [NMRC/0916/2004]
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 non-synonymous 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.
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