MDR1 (ABCB1) polymorphisms: functional effects and clinical implications.

摘要: MDR1 gene encodes for P glycoprotein (P-gp), which plays an important role in bioavailability and cell-toxicity limitation of a wide range drugs xenobiotics. Three single nucleotide polymorphisms (SNPs) the coding region (C3435T, C1236T G2677T/A) are most widely studied SNPs have been related to substrate inhibitor-dependent functional modifications vitro studies reduced expression tissues. The three exhibit highest frequencies Asian Caucasians populations lowest African populations. In regard clinical implications SNPs, it was found large meta-analysis that C3435T SNP associated with slight increase susceptibility ulcerative colitis cancer tacrolimus pharmacokinetics platinum-based chemotherapy response lung cancer. On other hand, has shown controversial results many cases disease drug where no meta-analyses performed. There is less information about G2677T/A which, although investigated some diseases pharmacokinetics, very limited number published meta-analyses. Further should include analysis haplotype 1236T-2677T/A-3435T as well MDR1, transporters metabolizers may be outcome variable.