Relationship between the C3435T and G2677T(A) polymorphisms in theABCB1gene and P-glycoprotein expression in human liver.

The aim of the study was to determine whether a correlation exists betweenMDR1 (ABCB1)gene polymorphisms at positions 3435 (C3435T) and 2677 (G2677T(A)) and the expression of human hepatic P-glycoprotein (P-gp).P-gp protein expression in 26 human livers was assessed by Western blotting andABCB1mRNA expression was determined by real time RT-PCR. The C3435T and G2677T(A) polymorphisms were identified by RFLP and direct sequence analysis, respectively.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 ofABCB1mRNA 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 theABCB1gene. Exposure to a PXR ligand prior to death did not influence mRNA or protein expression.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 theABCB1gene, although our study is limited by a small sample size. [ABSTRACT FROM AUTHOR]