Estrogen Receptor 1 Gene rs22346939 and rs9340799 Variants are Associated with Major Depressive Disorder and its Clinical Features

Abstract

Objective: Major Depressive Disorder (MDD) is a major health problem worldwide. Estrogen interacts with the central nervous system and has been shown to affect anxiety and depressive behavior. Estrogen mediates its effects by connecting its receptors, estrogen receptors 1 and 2. The purpose of this case-control study was to clarify the association between MDD risk and estrogen receptor 1 (ESR1) gene variants.

Methods: This study included 245 individuals (125 MDD patients and 120 healthy controls). Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) technics were used for genotypingESR1XbaII (rs9340799) and PvuII (rs22346939) variants.

Results: There were statistically significant differences between the groups in terms of genotype frequencies of the ESR1PvuII (-397 T > C) variant (p = 0.049) but not for the XbaII (-351 A > G) variant (p > 0.05). However, a correlation was observed between MDD and ESR1XbaII variant after male participants were excluded (p = 0.028). Also, the high pain score of MDD patients was associated with the ESR1PvuII variant, especially in female patients (p = 0.021). According to the results of combined genotype analysis, AA-TC combined genotype was correlated with a decreased risk in patients with MDD compared to controls (p = 0.016), while the combined genotype of GGCC was associated with increased risk in the patients with MDD compared to controls (p = 0.042).

Conclusion: The two ESR1 variants were associated with MDD risk and its features in both individual and combined forms.

Keywords: Estrogen receptor 1; PCR-RFLP.; major depressive disorder; rs22346939; rs9340799; variant.