PT  - JOURNAL ARTICLE
AU  - Kang, Ho-Jin
AU  - Song, Im-Sook
AU  - Shin, Ho Jung
AU  - Kim, Woo-Young
AU  - Lee, Choong-Hee
AU  - Shim, Joo-Cheol
AU  - Zhou, Hong-Hao
AU  - Lee, Sang Seop
AU  - Shin, Jae-Gook
TI  - Identification and Functional Characterization of Genetic Variants of Human Organic Cation Transporters in a Korean Population
AID  - 10.1124/dmd.106.013581
DP  - 2007 Apr 01
TA  - Drug Metabolism and Disposition
PG  - 667--675
VI  - 35
IP  - 4
4099  - http://dmd.aspetjournals.org/content/35/4/667.short
4100  - http://dmd.aspetjournals.org/content/35/4/667.full
SO  - Drug Metab Dispos2007 Apr 01; 35
AB  - 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 Km values and a 10- to 20-fold decrease in Vmax 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. The American Society for Pharmacology and Experimental Therapeutics