Genetic variations of the ABCC2 gene in the Chinese, Malay, and Indian populations of Singapore.
MRP2 is a drug transporter that is responsible for the gastrointestinal absorption and biliary excretion of a wide variety of endogenous and xenobiotic compounds, including many clinically used drugs. This study aims to identify genetic variations of ABCC2 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-two genetic variations of ABCC2, including 8 novel ones, were found: 1 in the 5' untranslated region, 10 in the coding exons (8 nonsynonymous and 2 synonymous variations), and 11 in the introns. Three novel nonsynonymous variations: 2686G > A (Glu896Lys), 4240C > T (His1414Tyr) and 4568A > C (Gln1523Pro) were detected in single heterozygous Malay, Chinese, and Indian subjects, respectively. Among the novel nonsynonymous variations, 4240C > T and 4568A > C were predicted to be functionally significant. These data would provide fundamental and useful information for pharmacogenetic studies on drugs that are substrates of MRP2 in Asians.
Ho
Woon Fei
WF
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Koo
Seok Hwee
SH
Yee
Jie Yin
JY
Lee
Jon Deoon
JD
D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics*; D002681:China / Q000208:ethnology; D005006:Ethnicity; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007194:India / Q000208:ethnology; D008296:Malaysia / Q000208:ethnology; D008297:Male; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012846:Singapore
D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C000715087:ABCC2 protein, human