title: Genetic variations of the SLC22A5 gene in the Chinese and Indian populations of Singapore.
abstract: 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.
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597.
authors.forename: Dorothy Su Lin
authors.initials: DS
authors.lastname: Toh
authors.forename: Jie Yin
authors.initials: JY
authors.lastname: Yee
authors.forename: Seok Hwee
authors.initials: SH
authors.lastname: Koo
authors.forename: Michael
authors.initials: M
authors.lastname: Murray
authors.forename: Edmund Jon Deoon
authors.initials: EJ
authors.lastname: Lee
mesh_terms: 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
chemical_list: D027701:Organic Cation Transport Proteins; C492020:SLC22A5 protein, human; D000074058:Solute Carrier Family 22 Member 5