Plasminogen activator inhibitor-1 gene is associated with major depression and antidepressant treatment response

Abstract

Evidence suggests that plasminogen activator inhibitor type 1 gene (SERPINE1) is a stress-related gene and serum plasminogen activator inhibitor type 1 levels are increased in patients with major depressive disorders (MDD). To investigate whether common genetic variation in the SERPINE1 gene is associated with MDD and the therapeutic response to antidepressants, six polymorphisms (rs2227631, rs1799889, rs6092, rs6090, rs2227684 and rs7242) of the SERPINE1 gene were genotyped in 188 Chinese MDD patients and 346 controls. Among the MDD patients, 140 accepted selective serotonin reuptake inhibitor (fluoxetine or citalopram) antidepressant treatment for 4 weeks with therapeutic evaluation before and after. In single-marker-based analysis, the rs2227684-G and rs7242-T alleles were more frequent in MDD patients than in controls (P=0.010 and 0.010, respectively). The haplotype derived from the rs6090-G, rs2227684-G and rs7242-T polymorphisms was 1.19-fold higher in patients with MDD than in controls (P=0.0038). Haplotype analysis in responders (defined as a 50% reduction of the initial Hamilton score) and nonresponders after 4 weeks of antidepressant treatment showed that the haplotype derived from the rs2227631-G and rs1799889-4G polymorphisms was lower in responders than nonresponders (11.4 vs. 22.4%, P=0.014). Our findings show, for the first time, that SERPINE1 genetic variants may play a role in MDD susceptibility and in the acute therapeutic response to selective serotonin reuptake inhibitors.