Abstract
Background
Organic anion transporters (OATs) play an essential role in the disposition of numerous organic anions. To clarify the interindividual variation in the function of OATs, genetic polymorphisms of the SLC22A6 and SLC22A7 in Korean subjects were investigated and associated with hepatic hOAT2 expression and the SLC22A7 genotype.Methods
The genetic variants and their frequencies for the SLC22A6 and SLC22A7 genes in 50 Korean subjects were investigated by direct sequencing. The expression of hOAT2 protein from 34 human liver samples was examined by western blot analysis.Results
Eight SNPs including 2 novel SNPs were identified in the SLC22A6 gene and eight SNPs including 4 novel SNPs were identified in the SLC22A7 gene. No amino acid alteration was found. Linkage disequilibrium (LD) analysis revealed that the SLC22A6 and SLC22A7 genes have separated single LD blocks and consist of a limited number of haplotypes (14 haplotypes for SLC22A6 and 5 haplotypes for SLC22A7). The expression of the hOAT2 protein varied 10-fold among 34 human livers but was not associated with the SLC22A7 genotype (p=0.16).Conclusions
The SLC22A7 genomic sequences showed low variability. A 10-fold variation in hOAT2 protein expression in the liver specimens was not correlated with SLC22A7 genotypes. These results suggest that genetic polymorphisms may not be a significant contributing factor to variations in the hOAT2 expression or hOAT2 transport activity.References
Articles referenced by this article (37)
Novel slc22 transporter homologs in fly, worm, and human clarify the phylogeny of organic anion and cation transporters.
Physiol Genomics, (1):12-24 2004
MED: 15054140
The multispecific organic anion transporter (OAT) family.
Pflugers Arch, (3):337-350 2000
MED: 10954321
Implications of genetic polymorphisms in drug transporters for pharmacotherapy.
Cancer Lett, (1):4-33 2006
MED: 16504381
Interindividual variability of canalicular ATP-binding-cassette (ABC)-transporter expression in human liver.
Hepatology, (1):62-74 2006
MED: 16799996
Pharmacogenomics: translating functional genomics into rational therapeutics.
Science, (5439):487-491 1999
MED: 10521338
Estimating the contribution of genes and environment to variation in renal drug clearance.
Pharmacogenetics, (9):581-584 2003
MED: 12972957
Variability in renal clearance of substrates for renal transporters in chinese subjects.
J Clin Pharmacol, (2):157-163 2006
MED: 16432267
Novel single nucleotide polymorphisms of organic cation transporter 1 (SLC22A1) affecting transport functions.
Biochem Biophys Res Commun, (3):789-793 2004
MED: 14697261
Identification of genetic variations of the human organic cation transporter hOCT1 and their functional consequences.
Pharmacogenetics, (8):591-595 2002
MED: 12439218
Show 10 more references (10 of 37)
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Funding
Funders who supported this work.
Korea Science and Engineering Foundation
Ministry of Education, Science and Technology (1)
Grant ID: R13-2007-023-00000-0
Ministry of Health and Welfare (1)
Grant ID: A030001