QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: dmd.106.013581v1 35/4/667    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kang, H.-J. Articles by Shin, J.-G. Search for Related Content PubMed PubMed Citation Articles by Kang, H.-J. Articles by Shin, J.-G.

Identification and Functional Characterization of Genetic Variants of Human Organic Cation Transporters in a Korean Population

Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Korea (H.-J.K., I.-S.S., H.J.S., W.-Y.K., C.-H.L., J.-C.S., S.S.L., J.-G.S.); and Institute of Clinical Pharmacology, Xiang-Ya School of Medicine, Central South University, Changsha, China (H.-H.Z.)

Genetic variants of three human organic cation transporter genes (hOCTs) were extensively explored in a Korean population. The functional changes of hOCT2 variants were evaluated in vitro, and those genetic polymorphisms of hOCTs were compared among different ethnic populations. From direct DNA sequencing, 7 of 13 coding variants were nonsynonymous single-nucleotide polymorphisms (SNPs), including four variants from hOCT1 (F160L, P283L, P341L, and M408V) and three from hOCT2 (T199I, T201M, and A270S), whereas 6 were synonymous SNPs. The linkage disequilibrium analysis presented for three independent LD blocks for each hOCT gene showed no significant linkage among all three hOCT genes. The transporter activities of MDCK cells that overexpress the hOCT2-T199I, -T201M, and -A270S variants showed significantly decreased uptake of [³H]methyl-4-phenylpyridinium acetate (MPP⁺) or [¹⁴C]tetraethylammonium compared with those cells that overexpress wild-type hOCT2, and the estimated kinetic parameters of these variants for [³H]MPP⁺ uptake in oocytes showed a 2- to 5-fold increase in K_m values and a 10- to 20-fold decrease in V_max values. The allele frequencies of the five functional variants hOCT1-P283L, -P341L, and hOCT2-T199I, -T201M, and -A270S were 1.3, 17, 0.7, 0.7, and 11%, respectively, in a Korean population; the frequency distributions of these variants were not significantly different from those of Chinese and Vietnamese populations. These findings suggest that genetic variants of hOCTs are not linked among three genes in a Korean population, and several of the hOCT genetic variants cause decreased transport activity in vitro compared with the wild type, although the clinical relevance of these variants remains to be evaluated.

This article has been cited by other articles:

				O. Zolk, T. F. Solbach, J. Konig, and M. F. Fromm Functional Characterization of the Human Organic Cation Transporter 2 Variant p.270Ala>Ser Drug Metab. Dispos., June 1, 2009; 37(6): 1312 - 1318. [Abstract] [Full Text] [PDF]