Li Cuifen, Xie Manli, Wang Weiwei, Liu Yanyan, Liao Dan, Yin Jingwen, Huang Hao
Department of Gynecology, Songshan Lake Central Hospital of Dongguan City, Dongguan, China.
Department of Obstetrics and Gynecology, Qingxi Hospital of Dongguan City, Dongguan, China.
Front Genet. 2022 Jul 19;13:936296. doi: 10.3389/fgene.2022.936296. eCollection 2022.
It is suggested that estrogen receptors (ERs) might be associated with the disproportionate vulnerability of women to depressive episodes. Several variants in ER-alpha (ERα) and ER-beta (ERβ) have been linked to depression, but the results were not consistent. Hence, we conducted a meta-analysis to evaluate the association between ERα/ERβ and depression in a cohort of women. A comprehensive literature search was performed in public databases. The genetic association between polymorphisms in Erα/ERβ and depression risk in a cohort of women was evaluated by odds ratios (ORs) and 95% confidence intervals (CIs). Cochran's Q test and the I index were used to evaluate heterogeneity. In total, 10 studies and 4 SNPs (rs2234693, rs9340799, rs4986938, rs1256049) were included in our meta-analysis. rs2234693 genotype was significantly associated with the risk of depression in women by dominant model (CC + CT vs TT, OR = 1.30, 95% CI: 1.09-1.55, = 0.0031), recessive model (CC vs CT + TT, OR = 1.64, 95% CI: 1.00-2.67, = 0.0478), additive model (CC vs TT, OR = 1.93, 95% CI: 1.12-3.35, = 0.0189) and allelic model (C vs T, OR = 1.24, 95% CI: 1.10-1.39, = 0.0003). For rs9340799, the frequencies of risk genotypes according to the dominant (GG + GA vs AA, OR = 1.47, 95% CI = 1.10-1.98, = 0.0096, I = 0%, = 0.43) and allelic (G vs A, OR = 1.33, 95% CI: 1.04-1.69, = 0.0236, I = 0%, = 0.39) models were significantly lower in women with depression than in controls within the Asian subgroup. For rs1256049, risk genotypes were significantly more frequent in depressed subjects than in controls under the dominant model (AA+ GA vs GG, OR = 1.62, 95% CI: 1.19-2.21, = 0.0024) and the allelic model (A vs G, OR = 1.35, 95% CI: 1.07-1.72, = 0.012) after sensitivity analysis by omitting one study which induce the heterogeneity. The current meta-analysis is the first and most comprehensive investigation of the association between ERs and depression in women, and the findings support the concept that ERs participate in the etiology of sex heterogeneity in depression.
有研究表明，雌激素受体（ERs）可能与女性更容易患抑郁症有关。雌激素受体α（ERα）和雌激素受体β（ERβ）的几种变体已被证明与抑郁症有关，但结果并不一致。因此，我们进行了一项荟萃分析，以评估女性群体中ERα/ERβ与抑郁症之间的关联。我们在公共数据库中进行了全面的文献检索。通过优势比（ORs）和95%置信区间（CIs）评估了Erα/ERβ基因多态性与女性群体抑郁症风险之间的遗传关联。采用Cochran's Q检验和I指数评估异质性。我们的荟萃分析共纳入了10项研究和4个单核苷酸多态性（SNP）（rs2234693、rs9340799、rs4986938、rs1256049）。rs2234693基因型在显性模型（CC + CT 与 TT 相比，OR = 1.30，95% CI：1.09 - 1.55，P = 0.0031）、隐性模型（CC 与 CT + TT 相比，OR = 1.64，95% CI：1.00 - 2.67，P = 0.0478）、加性模型（CC 与 TT 相比，OR = 1.93，95% CI：1.12 - 3.35，P = 0.0189）和等位基因模型（C 与 T 相比，OR = 1.24，95% CI：1.10 - 1.39，P = 0.0003）下与女性抑郁症风险显著相关。对于rs9340799，在亚洲亚组中，根据显性模型（GG + GA 与 AA 相比，OR = 1.47，95% CI = 1.10 - 1.98，P = 0.0096，I² = 0%，P = 0.43）和等位基因模型（G 与 A 相比，OR = 1.33，95% CI：1.04 - 1.69，P = 0.0236，I² = 0%，P = 0.39），抑郁症女性中风险基因型的频率显著低于对照组。对于rs1256049，在排除一项导致异质性的研究后进行敏感性分析，在显性模型（AA + GA 与 GG 相比，OR = 1.62，95% CI：1.19 - 2.21，P = 0.0024）和等位基因模型（A 与 G 相比，OR = 1.35，95% CI：1.07 - 1.72，P = 0.012）下，抑郁症患者中风险基因型的频率显著高于对照组。当前的荟萃分析是对女性中ERs与抑郁症关联的首次也是最全面的研究，研究结果支持ERs参与抑郁症性别异质性病因的观点。
