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. 2022 Jul 19:13:936296.
doi: 10.3389/fgene.2022.936296. eCollection 2022.

Association Between Polymorphisms in Estrogen Receptor Genes and Depression in Women: A Meta-Analysis

Cuifen Li  1 , Manli Xie  2 , Weiwei Wang  3 , Yanyan Liu  1 , Dan Liao  1 , Jingwen Yin  4 , Hao Huang  5
Affiliations

Association Between Polymorphisms in Estrogen Receptor Genes and Depression in Women: A Meta-Analysis

Cuifen Li et al. Front Genet. .

Abstract

Objective: 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. Methods: 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 I2 index were used to evaluate heterogeneity. Results: 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, p = 0.0031), recessive model (CC vs CT + TT, OR = 1.64, 95% CI: 1.00-2.67, p = 0.0478), additive model (CC vs TT, OR = 1.93, 95% CI: 1.12-3.35, p = 0.0189) and allelic model (C vs T, OR = 1.24, 95% CI: 1.10-1.39, p = 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, p = 0.0096, I2 = 0%, p = 0.43) and allelic (G vs A, OR = 1.33, 95% CI: 1.04-1.69, p = 0.0236, I2 = 0%, p = 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, p = 0.0024) and the allelic model (A vs G, OR = 1.35, 95% CI: 1.07-1.72, p = 0.012) after sensitivity analysis by omitting one study which induce the heterogeneity. Conclusions: 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.

Keywords: ERα; Erβ; depression; polymorphism; women.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
PRISMA flow chart of the inclusion and exclusion of studies. PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
FIGURE 2
FIGURE 2
(A), Forest plot of studies comparing the risk of the rs2234693 polymorphism of ERα between women with depression and controls; (B), Meta-analysis with a fixed-effects model with individual studies omitted.
FIGURE 3
FIGURE 3
Forest plot of studies comparing the distribution of the rs9340799 polymorphism of ERα between women with depression and controls.
FIGURE 4
FIGURE 4
(A), Forest plot of studies comparing the distribution of the rs9340799 polymorphism of ERα between women with depression and controls in the Asian subgroup. (B), The sensitivity analysis of the studies pooled in the meta-analysis of rs9340799 polymorphism and women with depression in Asian subgroup by omitting one study at a time.
FIGURE 5
FIGURE 5
Forest plot of studies comparing the distribution of the rs1256049 polymorphism of ERβ between women with depression and controls after the omission of Kang’s study.
See this image and copyright information in PMC

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References

    1. Baghel K., Srivastava R. (2020). Effect of Estrogen and Stress on Estrogen Receptor 1 in the HPG axis of Immature Male Gallus gallus Domesticus: Involvement of Anti-oxidant System. Theriogenology 155, 98–113. 10.1016/j.theriogenology.2020.05.048 - DOI - PubMed
    1. Blazer D. G. (2003). Depression in Late Life: Review and Commentary. Journals Gerontology Ser. A Biol. Sci. Med. Sci. 58 (3), M249–M265. 10.1093/gerona/58.3.m249 - DOI - PubMed
    1. Brand B. A., de Boer J. N., Sommer I. E. C. (2021). Estrogens in Schizophrenia: Progress, Current Challenges and Opportunities. Curr. Opin. Psychiatry 34 (3), 228–237. 10.1097/yco.0000000000000699 - DOI - PMC - PubMed
    1. Dwyer J. B., Aftab A., Radhakrishnan R., Widge A., Rodriguez C. I., Carpenter L. L., et al. (2020). Hormonal Treatments for Major Depressive Disorder: State of the Art. Am. J. Psychiatry 177 (8), 686–705. 10.1176/appi.ajp.2020.19080848 - DOI - PMC - PubMed
    1. Egger M., Smith G. D., Schneider M., Minder C. (1997). Bias in Meta-Analysis Detected by a Simple, Graphical Test. Bmj 315 (7109), 629–634. 10.1136/bmj.315.7109.629 - DOI - PMC - PubMed

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