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

- The rs10877887CC in promoter of let-7i was associated with an increased risk of MDD.
- The rs13293512CC in promoter of let-7a-1/let-7f-1/let-7d cluster increased MDD risk.
- Patients with rs13293512 TC and CC had increased risks of MDD recurrence.

BackgroundLet-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.MethodPolymerase 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.ResultsWe 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).LimitationsRelatively small sample size and hospital-based study design may influence the results.ConclusionsOur findings suggest that the rs10877887 and rs13293512 polymorphisms may be related to the development of MDD.