Zhang Xueying, Han Ying, Liu Xuhao, Chen Jin, Yuan Zhengrong, Wang Yajie
College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China.
Department of Clinical Laboratory, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China.
J Affect Disord. 2023 May 1;328:312-323. doi: 10.1016/j.jad.2023.02.001. Epub 2023 Feb 4.
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.
许多研究已对多巴胺D2受体（DRD2）基因中的遗传变异作为创伤后应激障碍（PTSD）和重度抑郁症（MDD）的风险因素进行了评估。然而，结果并不一致。本荟萃分析旨在系统总结已发表的数据，以评估DRD2基因变异与PTSD和MDD风险之间的可靠关联。
在2022年1月1日前，使用Web of Science、PubMed、谷歌学术、医学文摘数据库（EMBASE）、施普林格、ScienceDirect、Wiley Online Library、Cochrane对照试验中心注册库、中国生物医学文献数据库（CBM）、万方数据、维普资讯和中国知网数据库进行了系统的文献检索。
共检索到DRD2基因中的27个遗传变异，其中7个符合荟萃分析的纳入标准。我们的荟萃分析结果表明，rs1800497（TaqIA）多态性与PTSD风险增加显著相关（显性模型（A1A1 + A1A2 vs. A2A2）：OR = 1.49，95%CI，1.08 - 2.04，Z = 2.46，P = 0.014）。种族亚组分析表明，亚洲人（显性模型（A1A1 + A1A2 vs. A2A2）：OR = 1.39，95%CI，1.08 - 1.79，Z = 2.60，P = 0.009）和高加索人（显性模型（A1A1 + A1A2 vs. A2A2）：OR = 1.87，95%CI 1.02 - 3.41，Z = 2.04，P = 0.042）中观察到PTSD风险显著增加。同时，我们检测到DRD2基因中的rsl799978和rs2075652多态性与MDD之间存在显著的关联强度（对于rs1799978，纯合子比较（GG vs. AA）：OR = 0.60，95%CI = 0.37 - 0.97，Z = 2.08，P = 0.038；对于rs2075652，纯合子比较（AA vs. GG）：OR = 1.82，95%CI = 1.32 - 2.50，Z = 3.67，P < 0.001）。我们的累积荟萃分析表明，与PTSD和MDD的关联强度呈持续趋势。
本荟萃分析表明，DRD2基因变异可能潜在地导致PTSD和MDD的遗传易感性。将DRD2基因变异用作PTSD和MDD的风险因素需要通过大型精心设计
