Abstract

13072 Background: MRP2, encoded by ABCC2, is an ATP-binding cassette transporter that plays a critical role in the biliary elimination of various drugs and xenobiotics. Although SNPs in this gene have been identified and reported, their functions are not fully understood. T he purpose of this study was to evaluate the effect of polymorphisms/haplotypes of the ABCC2 gene on its mRNA expression in human liver. Methods: Two hundred human liver samples were genotyped for the following polymorphisms: −1549G>A, −1019A>G, −24C>T, 1249G>A (V417I), −34T>C (intron 27) and 3972C>T. Haplotypes and diplotypes were predicted and assigned to each individual. Haplotype-specific expression was then tested using 3972C>T and 1249G>A as markers. Heterozygous Caucasian samples for 3972C>T and 1249G>A were selected and the two SNPs were genotyped in the PCR and/or RT-PCR products from both DNA and the corresponding mRNA. The minisequencing-based SNaPshot method was used to genotype and quantify the expression level of each allele. The relative expression of both alleles in the mRNA was normalized to that in the DNA. Results: There is no haplotype-specific expression discriminated by the 3972C>T polymorphism. However, when using 1249G>A as a marker, the haplotypes containing the 1249A allele had significantly higher mRNA levels when compared with haplotypes containing the 1249G allele (one sample t test, p < 0.001, n = 37). Conclusions: The 1249G>A substitution in the ABCC2 gene may be associated with gene expression in human liver. Significant variability of the relative expression of ABCC2 in the population suggests that other functional polymorphisms and environmental factors may also be involved in the regulation of ABCC2 expression. No significant financial relationships to disclose.

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