The interaction of miR-34b/c polymorphisms and negative life events increases susceptibility to major depressive disorder in Han Chinese population

Abstract

BackgroundPrevious studies have shown that microRNAs(miRNAs) are involved in the pathogenesis of MDD; in particular, miR-34b/c has been implicated in MDD risk and found to exert antidepressant effects. However, the effects of miR-34b/c polymorphisms on MDD risk have not been investigated. MethodsIn this study, we evaluated the effect of miR-34b/c gene polymorphisms and their interaction with negative life events in relation to MDD, using data from 381 Han Chinese patients with MDD and 291 healthy volunteers. Allelic, genotypic, haplotypic, and gene-environment associations were analyzed using UNPHASED and SPSS software. ResultsAfter discarding data with extremely severe negative life events in our study population, we found an association between rs4938723, rs2187473 polymorphisms and MDD in the dominant models (TC/CC vs. TT, OR=1.45, P=0.027; TC/CC vs. TT, OR=3.32, P=0.030). In haplotype analysis, the C-G haplotype (rs4938723/rs28757623) showed the strongest association with MDD (OR=1.95, P=0.026). Additionally, we found significant gene-environment combination rs4938723 C allele, rs28757623 G allele and high level of negative life events (C-G-HN) was significantly associated with MDD (OR, 3.85; 95% CI, 1.62–9.13). In addition, the combination of (C-C-HN) is of significance (OR, 2.99; 95% CI, 1.36–6.60), indicating that the rs28757623 C allele may contribute to the risk of MDD as well. LimitationsThe sample size was small and the role of miR-34b/c polymorphisms for MDD should be assessed using independent samples from other ethnic populations. Conclusions: Our results suggest that miR-34b/c is a susceptibility factor for MDD stratified by negative life events and that rs4938723 is a significant association locus for gene-environment interaction in relation to MDD risk.