Genetic variations of the SLC22A5 gene in the Chinese and Indian populations of Singapore.
Novel organic cation transporter 2 (OCTN2) is a multispecific, bidirectional, pH-dependent organic cation transporter. It can function as a carnitine co-transporter with higher affinity for carnitine than OCTN1 but also functions as a uniporter for other cations. Drugs such as verapamil, pyrilamine and beta-lactam antibiotics have been characterized as substrates of OCTN2 and/or inhibitors of carnitine transport. This study identified variants of the SLC22A5 gene in two distinct ethnic groups of the Singaporean population (n=192) by DNA sequencing. Twenty-eight genetic variants of SLC22A5, including 13 that were novel, were found: 14 were located in the coding exons, 10 in the introns, 1 in the promoter region, 2 in the 5'-untranslated region and 1 in the 3'-untranslated region. Among the novel nonsynonymous variants, Asp122Tyr was predicted to be functionally significant. Functional nonsynonymous variants detected include Ser467Cys and Arg254X; the latter resulted in a premature stop codon and is predicted to result in a truncated protein that is less than half the molecular mass of wild-type OCTN2. These data constitute fundamental information of value for future pharmacogenetic studies in Asian populations on drugs that are substrates of OCTN2.
Toh
Dorothy Su Lin
DS
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597.
Yee
Jie Yin
JY
Koo
Seok Hwee
SH
Murray
Michael
M
Lee
Edmund Jon Deoon
EJ
D002681:China / Q000208:ethnology; D014644:Genetic Variation; D006801:Humans; D007194:India / Q000208:ethnology; D008958:Models, Molecular; D027701:Organic Cation Transport Proteins / Q000235:genetics*; D012846:Singapore; D000074058:Solute Carrier Family 22 Member 5
D027701:Organic Cation Transport Proteins; C492020:SLC22A5 protein, human; D000074058:Solute Carrier Family 22 Member 5