Assessment of genetic variants in D2 dopamine receptor (DRD2) gene as risk factors for post-traumatic stress disorder (PTSD) and major depressive disorder (MDD): A systematic review and meta-analysis

Many studies have performed assessments of genetic variants in the D2 dopamine receptor (DRD2) gene as risk factors for post-traumatic stress disorder (PTSD) and major depressive disorder (MDD). However, the results are inconsistent. This meta-analysis aimed to systematically summarize published data to evaluate the reliable association between the DRD2 genetic variants and the risk of PTSD and MDD.A systematic literature search was conducted using the Web of Science, PubMed, Google Scholar, Excerpta Medica Database (EMBASE), Springer, ScienceDirect, Wiley Online Library, Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature Database (CBM), WANFANG Data, CQVIP, and Chinese National Knowledge Infrastructure (CNKI) databases before January 1st, 2022.A total of 27 genetic variants in the DRD2 gene were retrieved, and 7 of them met the inclusion criteria for meta-analysis. Our meta-analysis results indicated that the rs1800497 (TaqIA) polymorphism was significantly associated with the increased risk of PTSD (Dominant model (A1A1 + A1A2 vs. A2A2): OR = 1.49, 95 % CI, 1.08-2.04 Z = 2.46, P = 0.014). Subgroup analysis for ethnicity suggested that a significantly increased risk of PTSD was observed in Asians (Dominant model (A1A1 + A1A2 vs. A2A2): OR = 1.39, 95 % CI, 1.08-1.79, Z = 2.60, P = 0.009) and Caucasians (Dominant model (A1A1 + A1A2 vs. A2A2): OR = 1.87, 95 % CI 1.02-3.41, Z = 2.04, P = 0.042). Meanwhile, we detected significant association strengths between the rs1799978 and rs2075652 polymorphisms in the DRD2 gene and MDD (for rs1799978, Homozygote comparison (GG vs. AA): OR = 0.60, 95 % CI = 0.37-0.97, Z = 2.08, P = 0.038; for rs2075652, Homozygote comparison (AA vs. GG): OR = 1.82, 95 % CI = 1.32-2.50, Z = 3.67, P < 0.001). Our cumulative meta-analyses indicated a continuous trend toward association strength with PTSD and MDD.This meta-analysis indicated that genetic variants in the DRD2 gene might potentially contribute to genetic susceptibility for PTSD and MDD. The utilization of DRD2 genetic variants as risk factors for PTSD and MDD requires further validation by large well-designed case-control studies.