内源性大麻素受体基因（CNR1和CNR2）多态性与抑郁症的关联：一项荟萃分析。
The association of endocannabinoid receptor genes (CNR1 and CNR2) polymorphisms with depression: A meta-analysis.
作者信息
Kong Xiangjuan, Miao Qingshan, Lu Xiaozi, Zhang Zeng, Chen Min, Zhang Jinxiang, Zhai Jinguo
机构信息
Department of Clinical Psychology, Jining Psychiatric Hospital.
Department of Clinical Psychology, Qindao Mental Health Center.
出版信息
Medicine (Baltimore). 2019 Nov;98(46):e17403. doi: 10.1097/MD.0000000000017403.
Studies investigating the association between gene variants and depression susceptibility found inconsistent data. The present study aimed to clarify whether CNR1rs1049353, CNR1 AAT triplet repeat, and CNR2rs2501432 polymorphisms confer higher risk for depressive disorder.Literature from PubMed, Medline, Embase, Scopus, Cochrance Library, and Wanfang databases was searched (up to August 20, 2018). Seven case-control studies with various comorbidities were eligible. We targeted CNR single-nucleotide polymorphisms (SNPs) that have been reported by 2 or more studies to be involved in the current meta-analysis, resulting in a final list of 3 SNPs: CNR1rs1049353, CNR1 AAT triplet repeat polymorphism, and CNR2rs2501432. Odds ratios (ORs) and 95% confidence intervals (CIs) for allele and homozygote comparisons, dominant and recessive models, and triplet repeat polymorphism ((AAT)n≥5, ≥5 vs (AAT)n<5, <5 or <5, ≥5) were assessed using a random effect model as measures of association. Heterogeneity among included studies was analyzed using sensitivity test. Publication bias was also explored by Egger and rank correlation test.overall, no significant association was found between depression and CNR1rs1049353 (G vs A: OR [95% CI] = 1.09 [0.61-1.95]; GG vs AA: 1.29 [0.73-2.26]; GG vs GA+AA: 1.10 [0.57-2.10]; GG+GA vs AA: 1.25 [0.72-2.18]; and AAT triplet repeat polymorphism ((AAT)n≥5, ≥5 vs (AAT)n<5, <5 or <5, ≥5): 1.92 [0.59-6.27]. In contrast, a significant association between CNR2rs2501432 and depression was detected, and the ORs and 95% CIs are as follows: allele contrast (OR = 1.39, 95% CI = [1.12-1.72], P = .003); homozygous (OR = 2.19, 95% CI = [1.34-3.59], P = .002); dominant (OR = 1.93,95% CI = [1.23-3.04], P = .005); and recessive (OR = 1.41, 95% CI = [1.04-1.92], P = .03).This meta-analysis revealed that CNR1rs1049353 or AAT triplet repeat polymorphism had no association with susceptibility to depression, while CNR2rs2501432 polymorphism was a remarkable mark for depression patients.
研究基因变异与抑郁症易感性之间关联的数据并不一致。本研究旨在阐明CNR1rs1049353、CNR1 AAT三联体重复序列以及CNR2rs2501432多态性是否会增加患抑郁症的风险。我们检索了PubMed、Medline、Embase、Scopus、Cochrance图书馆以及万方数据库中的文献（截至2018年8月20日）。七项包含各种合并症的病例对照研究符合要求。我们选取了两项或更多研究报道的与本次荟萃分析相关的CNR单核苷酸多态性（SNP），最终确定了3个SNP：CNR1rs1049353、CNR1 AAT三联体重复多态性以及CNR2rs2501432。使用随机效应模型评估等位基因和纯合子比较、显性和隐性模型以及三联体重复多态性（(AAT)n≥5，≥5与(AAT)n<5，<5或<5，≥5）的优势比（OR）和95%置信区间（CI）作为关联度量。采用敏感性检验分析纳入研究之间的异质性。通过Egger检验和秩相关检验探索发表偏倚。总体而言，未发现抑郁症与CNR1rs1049353之间存在显著关联（G与A：OR [95% CI] = 1.09 [0.61 - 1.95]；GG与AA：1.29 [0.73 - 2.26]；GG与GA + AA：1.10 [0.57 - 2.10]；GG + GA与AA：1.25 [0.72 - 2.18]；以及AAT三联体重复多态性((AAT)n≥5，≥5与(AAT)n<5，<5或<5，≥5)：1.92 [0.59 - 6.27]）。相比之下，检测到CNR2rs2501432与抑郁症之间存在显著关联，OR和95% CI如下：等位基因对比（OR = 1.39，95% CI = [1.12 - 1.72]，P = 0.003）；纯合子（OR = 2.19，95% CI = [1.34 - 3.59]，P = 0.002）；显性（OR = 1.93，95% CI = [1.23 - 3.04]，P = 0.005）；隐性（OR = 1.41，95% CI = [1.04 - 1.92]，P = 0.03）。这项荟萃分析表明，CNR1rs1049353或AAT三联体重复多态性与抑郁症易感性无关，而CNR2rs2501432多态性是抑郁症患者的一个显著标志。
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