Identification of genetic polymorphisms of human OAT1 and OAT2 genes and their relationship to hOAT2 expression in human liver

Clin Chim Acta. 2010 Jan;411(1-2):99-105. doi: 10.1016/j.cca.2009.10.015. Epub 2009 Oct 22.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Blotting, Western
  • DNA Primers
  • Genotype
  • Haplotypes
  • Humans
  • Linkage Disequilibrium
  • Liver / metabolism*
  • Organic Anion Transport Protein 1 / genetics*
  • Organic Anion Transporters, Sodium-Independent / genetics*
  • Polymorphism, Single Nucleotide*
  • Republic of Korea

Substances

  • DNA Primers
  • Organic Anion Transport Protein 1
  • Organic Anion Transporters, Sodium-Independent
  • SLC22A7 protein, human