ausblenden:
Schlagwörter:
P-glycoprotein, ABCB1, MDR1, antidepressant treatment, major depression
Zusammenfassung:
The efflux pump P-glycoprotein (P-gp), a gene product of the ABCB1 gene,
plays a pivotal role in the transfer of various molecules across the
blood-brain barrier. P-gp protects the brain by selectively extruding
its substrates, including certain antidepressive drugs, thereby limiting
their uptake into the brain. Uhr et al. [2008] first showed that ABCB1
variants predicted the remission to antidepressants with P-gp substrate
properties in patients suffering from major depression (MD). Other
studies investigating the influence of ABCB1 polymorphisms on
antidepressant treatment response produced inconclusive results. In this
meta-analysis, we systematically summarized 16 pharmacogenetic studies
focused on the association of ABCB1 variants and antidepressant
treatment outcome in patients with MD (overall n=2695). We investigated
the association of treatment outcome and six ABCB1 single nucleotide
polymorphisms (SNPs): rs2032583, rs2235015, rs2235040, rs1045642,
rs2032582, rs1128503. We stratified for admission status, ethnicity, and
prescription of concomitant medication. SNP rs2032583 showed a nominally
significant association across all studies (P=0.035, SNP was studied in
a total of 2,037 patients) and a significant Bonferroni-corrected
association among inpatients (P=1.5x10(-05), n=485). Also SNP rs2235015
was significantly associated with antidepressant treatment outcome
withstanding Bonferroni correction (P=3.0x10(-04)) among inpatients in a
smaller subsample (n=195). There were no significant associations of the
other SNPs tested with antidepressant treatment outcome. Future
pharmacogenetic association studies should focus on the role of the
ABCB1 SNP rs2032583 in antidepressant outcome prediction. (c) 2015 Wiley
Periodicals, Inc.
