Genetic variants in the promoters of let-7 family are associated with an increased risk of major depressive disorder.

Abstract Background Let-7 family plays a critical role in the pathogenesis of major depressive disorder (MDD). Genetic polymorphisms in the promoters of miRNA may influence individual׳s susceptibility to diseases. The purpose of this study was to investigate the association between rs10877887 and rs13293512 polymorphisms in the promoters of let-7 family and the risk of MDD. Method Polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing assays were used to analyze the rs10877887 and rs13293512 polymorphisms in 237 MDD patients and 296 controls. Results We found that the rs10877887 CC genotype was associated with an increased risk of MDD (CC vs. TT: OR=1.73, 95% CI, 1.04−2.86, P= 0.03, and CC vs. TT/TC: OR=1.74, 95% CI, 1.08–2.80, P= 0.02, respectively). Similarly increased risk was also observed for the rs13293512 (CC vs. TT: OR=1.83, 95% CI, 1.12–2.99, P= 0.015; CC vs. TT/TC: OR=1.84, 95% CI, 1.20–2.81, P= 0.005; and C vs. T: OR=1.32, 95% CI, 1.03–1.68, P= 0.03, respectively). Stratification analysis showed that patients with the rs13293512 TC and CC genotypes had a 2.29 and 2.56-fold increased risk of MDD recurrence after treatment (TC vs. TT: 95% CI, 1.23–4.25, P= 0.008; CC vs. TT: 95% CI, 1.25–5.23, P= 0.009, respectively). Limitations Relatively small sample size and hospital-based study design may influence the results. Conclusions Our findings suggest that the rs10877887 and rs13293512 polymorphisms may be related to the development of MDD.