AUTHOR=Han Wenxiu , Zhang Haixia , Gong Xiaoxue , Guo Yujin , Yang Mengqi , Zhang Hailiang , Zhou Xueyuan , Li Gongying , Liu Yuanyuan , Jiang Pei , Yan Genquan 

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

JOURNAL=Frontiers in Genetics

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2019.00921

DOI=10.3389/fgene.2019.00921

ISSN=1664-8021

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