The role of the N363S polymorphism of the human glucocorticoid receptor gene (NR3C1) in Turkish patients with major depressive disorder (MDD)

Abstract

Glucocorticoid receptor (GR) is one of the involved receptors and its gene has been recognized as a candidate gene for major depressive disorder and bipolar disorder. The involvement of the GR gene (NR3C1) locus on human chromosome 5q31-q32. The N363S (rs6195) is located within exon 2 and changes the second base of codon 363, leading to asparagine to serine substitution in the transactivation domain of GR. In this study, we aimed to examine the role of NR3C1 N363S polymorphisms in genetic susceptibility to MDD development in a Turkish population. A total of 100 consecutive unrelated adult patients with documented medical records of MDD were from outpatient Psychiatry Clinic in Gaziosmanpas a University Research and Training Hospital, Tokat, Turkey by referral from the treating physician, after obtaining initial verbal consent to participate in the study. In addition, 100 control subjects from the same area as the patients, and comprising blood donors, healthy volunteers were enrolled this study. DNA was isolated from peripheral blood samples and the N363S variant was screened by the RT-PCR technique. 99 out of the 100 MDD patients were found to be AA genotype at the N363S (AA genotype frequency 0.99; A-allele frequency 0.995). Also, 1 out of the 100 MDD patients was found to be AG genotype (AG genotype frequency 0.01; G-allele frequency 0.005). No homozygote for the rare G-allele was seen. Significantly more frequent occurrence of allele-A in N363S polymorphism was observed in the group of the patients with MDD in comparison with the control group (OR: 4.061, 95% CI: 0.449–36.660, v2 : 1.823, p: 0.177). For genotype AG versus AA, no significant correlation was demonstrated between patients and the control group with respect to the investigated SNP (OR: 0.242, 95% CI: 0.027–2.208, v2 : 1.846, p: 0.1742). This study was supported by the Gaziosmanpas a University Scientific Research Fund (GOU BAP2013/8).