Functional consequences of single nucleotide polymorphisms in the human organic anion transporter hOAT1 (SLC22A6). J Pharmacol Exp Ther 2005

The human organic anion transporter hOAT1 (SLC22A6) con-tributes to the uptake of a range of small organic anions across the basolateral membrane of the renal proximal tubule and drives their urinary elimination. The aim of this study was to identify genetic variants of hOAT1 and to investigate potential effects on the functional properties of this transporter. Twenty single nucleotide polymorphisms (SNPs) in hOAT1 were iden-tified in genomic DNA from 92 individuals of African, Asian, and Caucasian origin. Two SNPs encoded changes in amino acid sequence; arginine to histidine (residue 50) and lysine to iso-leucine (residue 525). Significantly, these SNPs were only present in the samples of African origin. When expressed in Xenopus oocytes, wild-type R50-hOAT1 and the variants R50H-hOAT1 and K525I-hOAT1 all mediated the probenecid