title: The Association Between Genetic Variants in the Dopaminergic System and Posttraumatic Stress Disorder: A Meta-Analysis.
abstract: Posttraumatic stress disorder (PTSD) is a complex mental disorder and can severely interfere with the normal life of the affected people. Previous studies have examined the association of PTSD with genetic variants in multiple dopaminergic genes with inconsistent results. To perform a systematic literature search and conduct meta-analysis to examine whether genetic variants in the dopaminergic system is associated with PTSD. Data Sources: PubMed, Cochrane Library, Embase, Google Scholar, and HuGE. Study eligibility criteria and participants: The studies included subjects who had been screened for the presence of PTSD; the studies provided data for genetic variants of genes involved in the dopaminergic system; the outcomes of interest included diagnosis status of PTSD; and the studies were case-control studies. Study appraisal and synthesis methods: Odds ratio was used as a measure of association. We used random-effects model in all the meta-analyses. Between-study heterogeneity was assessed using I², and publication bias was evaluated using Egger test. Findings from meta-analyses were confirmed using random-effects meta-analyses under the framework of generalized linear model (GLM). A total of 19 studies met the eligibility criteria and were included in our analyses. We found that rs1800497 in DRD2 was significantly associated with PTSD (OR = 1.96, 95% CI: 1.15-3.33; P = 0.014). The 3'-UTR variable number tandem repeat (VNTR) in SLC6A3 also showed significant association with PTSD (OR = 1.62, 95% CI: 1.12-2.35; P = 0.010), but there was no association of rs4680 in COMT with PTSD (P = 0.595). Sample size is limited for some studies; type and severity of traumatic events varied across studies; we could not control for potential confounding factors, such as age at traumatic events and gender; and we could not examine gene-environment interaction due to lack of data. We found that rs1800497 in DRD2 and the VNTR in SLC6A3 showed significant association with PTSD. Future studies controlling for confounding factors, with large sample sizes and more homogeneous traumatic exposure, are needed to validate the findings from this study.
authors.affiliation: From the Department of Critical Care and Emergency Medicine, The Affiliated Hospital of Hainan Medical University, Haikou, Hainan (LL); Emergency Department, Shengjing Hospital of China Medical University (LL, SH, GW, QL); Department of Neurosurgery, The First Hospital of China Medical University, Shenyang, Liaoning (YB, YG, PW, XH, ST, DZ, YW); Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China (DM); Rush Alzheimer's Disease Center (JY); and Department of Neurological Sciences (JY), Rush University Medical Center, Chicago, IL, USA.
authors.forename: Lizhuo
authors.initials: L
authors.lastname: Li
authors.forename: Yijun
authors.initials: Y
authors.lastname: Bao
authors.forename: Songbai
authors.initials: S
authors.lastname: He
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.forename: Yanlei
authors.initials: Y
authors.lastname: Guan
authors.forename: Dexuan
authors.initials: D
authors.lastname: Ma
authors.forename: Pengfei
authors.initials: P
authors.lastname: Wang
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Huang
authors.forename: Shanwei
authors.initials: S
authors.lastname: Tao
authors.forename: Dewei
authors.initials: D
authors.lastname: Zhang
authors.forename: Qiwen
authors.initials: Q
authors.lastname: Liu
authors.forename: Yunjie
authors.initials: Y
authors.lastname: Wang
authors.forename: Jingyun
authors.initials: J
authors.lastname: Yang
mesh_terms: D002394:Catechol O-Methyltransferase / Q000235:genetics*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D004299:Dopamine beta-Hydroxylase / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D013313:Stress Disorders, Post-Traumatic / Q000235:genetics*
chemical_list: C581293:DRD2 protein, human; D050483:Dopamine Plasma Membrane Transport Proteins; D017448:Receptors, Dopamine D2; C493214:SLC6A3 protein, human; D004299:Dopamine beta-Hydroxylase; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase