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

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.

Polymorphism of Estrogen Receptor Genes and Its Interactions With Neurodevelopmental Genes in Attention Deficit Hyperactivity Disorder Among Chinese Han Descent

“…Similarly, there was a trend for ESR1 gene rs6930355 to be associated with ADHD in females but not males. These findings align with previous studies showing that ESR genes affect the sex heterogeneity seen in psychiatric disorders [ 44 - 46 ]. Sexual dimorphism in ADHD has also been reported in our previous studies [ 47 , 48 ].…”

“…These findings align with previous studies showing that ESR genes affect the sex heterogeneity seen in psychiatric disorders. [44][45][46] Sexual dimorphism in ADHD has also been reported in our previous studies. 47,48 Prior work exploring the role of genes in the sexual dimorphism of ADHD has mainly focused on sex chromosomes and sex hormones.…”

Depression in Women: Potential Biological and Sociocultural Factors Driving the Sex Effect

“…Among biological aspects, specific genetic factors might play a role, based also on the familiarity of these conditions [24][25][26]. Among these, polymorphisms within genes encoding for the oestrogen receptor (ER) alpha and beta, in particular the rs2234693 single-nucleotide polymorphism (SNP) of ER alpha, have been proposed to be involved in the increased vulnerability of some women to "reproductive depression subtypes," as portrayed in a recent meta-analysis by Li and colleagues [27]. In comparison, a limited number of studies investigated the role of ER polymorphisms on depression in males, but these generally reported non-significant associations [28].…”