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CACNA1C rs1006737  is a novel variant in discovery of replicable associations in major depressive disorder (MDD). However, there have been no specific studies considered effect of environmental pathogens to date examining its clinical significance. In this study we investigated the interaction effect between  CACNA1C rs1006737  polymorphism and threatening life events (TLEs) in MDD and carried out a meta-analysis of published findings.    Methods  A total of 1,177 consecutive participants were genotyped. Information on exposure to TLEs, socio-demographic data, and history of psychological problems among first-degree relatives was collected. MDD was diagnosed according to the Chinese version of the 24-item Hamilton Rating Scale for Depression.    Results  There was a significant interaction effect between  CACNA1C rs1006737  polymorphism and TLEs in MDD. A dose–response relationship was found between  CACNA1C rs1006737  genotypes and TLEs in MDD. The results of the meta-analysis showed that  CACNA1C rs1006737  genotypes interacted with TLEs in MDD.    Conclusion   CACNA1C rs1006737  genotype and previous exposure to TLEs interact to influence the risk of developing MDD. We propose that  CACNA1C rs1006737  may represent a target for novel pharmacological therapies to prevent or treat MDD.

CACNA1C rs1006737, Threatening Life Events, and Gene–Environment Interaction Predict Major Depressive Disorder