Background: Both genetic and environmental factors as well as their interaction contribute to the etiology of major depressive disorder (MDD). Estrogen receptor β (ESR2) may play a vital role in the development of MDD in females. The aim of this study is to analyze ESR2 gene polymorphisms and the interaction of ESR2 gene variation and negative life events concerning the risk of developing MDD in females, especially during menopausal stage.
Methods: Genotyping was performed by Taqman allelic discrimination assay among 191 female MDD patients and 200 healthy females. Life Events Scale and the generalized multifactor dimensionality reduction method were employed to assess the frequency and severity of negative life events and gene-environment interaction (G×E), respectively. All subjects were regrouped into reproductive and menopausal group based on age. Logistic regression was used to evaluate the set of risk factors.
Results: No association of ESR2 G×E interaction with MDD was found in the reproductive group. However, in menopausal females, significant G×E interactions between negative life events and allelic variation of rs1256049 and rs4986938 were observed. Individuals with the A+ allele of rs1256049 and rs4986938 were susceptible to MDD when exposed to low negative life events.
Limitation: Assessment of negative life events was influenced by subjective interpretation.
Conclusions: ESR2 may modify the interaction between negative life events and MDD in the Chinese Han menopausal females. To our knowledge, this study is the first to report an effect modification between negative life events and ESR2 variations in female MDD patients.
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