Breitenstein Barbara, Brückl Tanja Maria, Ising Marcus, Müller-Myhsok Bertram, Holsboer Florian, Czamara Darina
HMNC GmbH, Munich, Germany.
Max Planck Institute of Psychiatry, Munich, Germany.
Am J Med Genet B Neuropsychiatr Genet. 2015 Jun;168B(4):274-83. doi: 10.1002/ajmg.b.32309. Epub 2015 Apr 2.
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 = 1.5 × 10(-05) , n = 485). Also SNP rs2235015 was significantly associated with antidepressant treatment outcome withstanding Bonferroni correction (P = 3.0 × 10(-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.
外排泵P-糖蛋白（P-gp）是ABCB1基因的产物，在各种分子穿越血脑屏障的过程中起关键作用。P-糖蛋白通过选择性地排出其底物（包括某些抗抑郁药物）来保护大脑，从而限制它们进入大脑。Uhr等人[2008年]首次表明，ABCB1变体可预测重度抑郁症（MD）患者对抗抑郁药物（具有P-糖蛋白底物特性）的缓解情况。其他研究ABCB1多态性对抗抑郁治疗反应影响的结果并不确定。在这项荟萃分析中，我们系统地总结了16项药物遗传学研究，这些研究聚焦于MD患者中ABCB1变体与抗抑郁治疗结果的关联（总体n = 2695）。我们研究了治疗结果与六个ABCB1单核苷酸多态性（SNP）的关联：rs2032583、rs2235015、rs2235040、rs1045642、rs2032582、rs1128503。我们按入院状态、种族和联合用药处方进行分层。SNP rs2032583在所有研究中显示出名义上的显著关联（P = 0.035，共有2037名患者研究了该SNP），在住院患者中经Bonferroni校正后具有显著关联（P = 1.5×10^(-05)，n = 485）。在一个较小的亚样本（n = 195）的住院患者中，SNP rs2235015经Bonferroni校正后也与抗抑郁治疗结果显著相关（P = 3.0×10^(-04)）。所测试的其他SNP与抗抑郁治疗结果均无显著关联。未来的药物遗传学关联研究应聚焦于ABCB1 SNP rs2032583在抗抑郁结果预测中的作用。
