The association of endocannabinoid receptor genes (CNR1 and CNR2) polymorphisms with depression: A meta-analysis

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.