Oo Khine Zin, Aung Ye Kyaw, Jenkins Mark A, Win Aung Ko
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Carlton, VIC, Australia The Park-Centre for Mental Health, Treatment, Research and Education, Wacol, QLD, Australia.
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Carlton, VIC, Australia.
Aust N Z J Psychiatry. 2016 Sep;50(9):842-57. doi: 10.1177/0004867416637920. Epub 2016 Mar 15.
The neurotransmitter serotonin is understood to control mood and drug response. Carrying a genetic variant in the serotonin transporter gene (5HTT) may increase the risk of major depressive disorder and alcohol dependence. Previous estimates of the association of the S allele of 5HTTLPR polymorphism with major depressive disorder and alcohol dependence have been inconsistent.
For the systematic review, we used PubMed MEDLINE and Discovery of The University of Melbourne to search for all relevant case-control studies investigating the associations of 5HTTLPR polymorphism with major depressive disorder and alcohol dependence. Summary odds ratios (OR) and their 95% confidence intervals (CI) were estimated. To investigate whether year of publication, study population or diagnostic criteria used were potential sources of heterogeneity, we performed meta-regression analyses. Publication bias was assessed using Funnel plots and Egger's statistical tests.
We included 23 studies of major depressive disorder without alcohol dependence containing 3392 cases and 5093 controls, and 11 studies of alcohol dependence without major depressive disorder containing 2079 cases and 2273 controls. The summary OR for homozygote carriers of the S allele of 5HTTLPR polymorphism compared with heterozygote and non-carriers combined (SS vs SL+LL genotype) was 1.33 (95% CI = [1.19, 1.48]) for major depressive disorder and 1.18 (95% CI = [1.01, 1.38]) for alcohol dependence. The summary OR per S allele of 5HTTLPR polymorphism was 1.16 (95% CI = [1.08, 1.23]) for major depressive disorder and 1.12 (95% CI = [1.01, 1.23]) for alcohol dependence. Meta-regression models showed that the associations did not substantially change after adjusting for year of publication, study population and diagnostic criteria used. There was no evidence for publication bias of the studies included in our meta-analysis.
Our meta-analysis confirms that individuals with the homozygous S allele of 5HTTLPR polymorphism are at increased risks of major depressive disorder as well as alcohol dependence. Further studies are required to investigate the association between 5HTTLPR polymorphism and the comorbidity of major depressive disorder and alcohol dependence as well as gene × environmental interactions.
神经递质血清素被认为可控制情绪和药物反应。携带血清素转运体基因（5HTT）的遗传变异可能会增加患重度抑郁症和酒精依赖症的风险。先前关于5HTTLPR多态性的S等位基因与重度抑郁症和酒精依赖症之间关联的估计并不一致。
为进行系统评价，我们使用PubMed MEDLINE和墨尔本大学的发现数据库搜索所有相关的病例对照研究，以调查5HTTLPR多态性与重度抑郁症和酒精依赖症之间的关联。估计汇总比值比（OR）及其95%置信区间（CI）。为调查发表年份、研究人群或所使用的诊断标准是否为异质性的潜在来源，我们进行了meta回归分析。使用漏斗图和Egger统计检验评估发表偏倚。
我们纳入了23项关于无酒精依赖的重度抑郁症的研究，其中包含3392例病例和5093例对照，以及11项关于无重度抑郁症的酒精依赖症的研究，其中包含2079例病例和2273例对照。与杂合子和非携带者组合（SS与SL + LL基因型）相比，5HTTLPR多态性的S等位基因纯合子携带者的汇总OR在重度抑郁症中为1.33（95% CI = [1.19, 1.48]），在酒精依赖症中为1.18（95% CI = [1.01, 1.38]）。5HTTLPR多态性每个S等位基因的汇总OR在重度抑郁症中为1.16（95% CI = [1.08, 1.23]），在酒精依赖症中为1.12（95% CI = [1.01, 1.23]）。Meta回归模型显示，在调整发表年份、研究人群和所使用的诊断标准后，关联没有实质性变化。我们的meta分析中纳入的研究没有发表偏倚的证据。
我们的meta分析证实，5HTTLPR多态性的纯合S等位基因个体患重度抑郁症和酒精依赖症的风险增加。需要进一步研究来调查5HTTLPR多态性与重度抑郁症和酒精依赖症的共病以及基因×环境相互作用之间的关联。
