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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 ( SGK1 ) is a stress-responsive gene with a pivotal role in both the heart and brain. To determine the role of  SGK1  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  SGK1  gene were successfully genotyped by polymerase chain reaction–ligase detection reaction (PCR-LDR) assay. Our results showed no significant differences in  SGK1  genetic polymorphisms between CHD patients and controls, whereas significant associations were observed between  SGK1  SNPs (rs1743963 and rs1763509) and the development of depression in CHD patients ( P  = 0.018 by genotype,  P  = 0.032 by allele;  P  = 0.017 by genotype,  P  = 0.003 by allele, respectively). However, none of these associations remained significant after Bonferroni correction ( P  = 0.054 for rs1743963;  P  = 0.051 for rs1763509). Interestingly, both the GG genotype of  SGK1  rs1743963 and AA genotype of  SGK1  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 ( P  = 0.008). Notably, haplotype analysis indicated that haplotype GGA significantly increased the risk of depression in CHD patients ( P  = 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 ( P  = 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 ( P  = 0.044) and that no significant differences were found for other  SGK1  SNPs (rs2758151, rs9493857, rs9376026, and rs9389154) between CHD patients with and without depression. These findings, for the first time, elucidate the important role of  SGK1  variants in the comorbidity of CHD and depression.

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