Relationship between the C3435T and G2677T(A) polymorphisms in the ABCB1 gene and P‐glycoprotein expression in human liver

Abstract

Aims The aim of the study was to determine whether a correlation exists between MDR1 (ABCB1) gene polymorphisms at positions 3435 (C₃₄₃₅T) and 2677 (G₂₆₇₇T(A)) and the expression of human hepatic P-glycoprotein (P-gp). Methods P-gp protein expression in 26 human livers was assessed by Western blotting and ABCB1 mRNA expression was determined by real time RT-PCR. The C₃₄₃₅T and G₂₆₇₇T(A) polymorphisms were identified by RFLP and direct sequence analysis, respectively. Results The C and G allele frequencies for the C₃₄₃₅T and G₂₆₇₇T(A) polymorphisms were 0.48 and 0.79, respectively, and the genotypes were in Hardy–Weinberg equilibrium. There was a 200- and 20-fold variation in the expression of ABCB1 mRNA and Pgp protein expression, respectively. There were no differences in mRNA and protein expression identified amongst the different genotypes attributable to the C₃₄₃₅T and G₂₆₇₇T(A) polymorphisms in the ABCB1 gene. Exposure to a PXR ligand prior to death did not influence mRNA or protein expression. Conclusions There is substantial variability in the expression of Pgp in human liver, but this is not due to the presence of C₃₄₃₅T and G₂₆₇₇T(A) polymorphisms in the ABCB1 gene, although our study is limited by a small sample size.