Association of SGK1 Polymorphisms With Susceptibility to Coronary Heart Disease in Chinese Han Patients With Comorbid Depression

Abstract

There is a strong link between heart disease and depression, both of which are closely related to lifetime stress exposure. Serum/glucocorticoid-regulated kinase 1 (<i>SGK1</i>) is a stress-responsive gene with a pivotal role in both the heart and brain. To determine the role of <i>SGK1</i> polymorphisms (rs2758151, rs1743963, rs9493857, rs1763509, rs9376026, and rs9389154) in susceptibility to comorbid coronary heart disease (CHD) and depression, we conducted a hospital-based case-control study involving 257 CHD cases (including 69 cases with depression and 188 cases without depression) and 107 controls in a Chinese Han population. Six single-nucleotide polymorphisms (SNPs) in the <i>SGK1</i> gene were successfully genotyped by polymerase chain reaction-ligase detection reaction (PCR-LDR) assay. Our results showed no significant differences in <i>SGK1</i> genetic polymorphisms between CHD patients and controls, whereas significant associations were observed between <i>SGK1</i> SNPs (rs1743963 and rs1763509) and the development of depression in CHD patients (<i>P</i> = 0.018 by genotype, <i>P</i> = 0.032 by allele; <i>P</i> = 0.017 by genotype, <i>P</i> = 0.003 by allele, respectively). However, none of these associations remained significant after Bonferroni correction (<i>P</i> = 0.054 for rs1743963; <i>P</i> = 0.051 for rs1763509). Interestingly, both the GG genotype of <i>SGK1</i> rs1743963 and AA genotype of <i>SGK1</i> rs1763509 were associated with a higher risk of depression in CHD patients; for rs1763509, the Patient Health Questionnaire-9 (PHQ-9) scores in the carriers of the risk genotype for comorbid depression, AA, were significantly higher than in GG and AG carriers (<i>P</i> = 0.008). Notably, haplotype analysis indicated that haplotype GGA significantly increased the risk of depression in CHD patients (<i>P</i> = 0.011, odds ratio (OR) = 1.717, 95% confidence interval (CI) = 1.132-2.605), whereas haplotype AAG may be a protective factor for CHD patients with comorbid depression (<i>P</i> = 0.038, OR = 0.546, 95% CI = 0.307-0.972). It should be noted that only the significance of haplotype GGA survived after Bonferroni adjustment (<i>P</i> = 0.044) and that no significant differences were found for other <i>SGK1</i> SNPs (rs2758151, rs9493857, rs9376026, and rs9389154) between CHD patients with and without depression. These findings, for the first time, elucidate the important role of <i>SGK1</i> variants in the comorbidity of CHD and depression.