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Front. Genet. | doi: 10.3389/fgene.2019.00921

Association of SGK1 polymorphisms with susceptibility to coronary heart disease in Chinese Han patients with comorbid depression

 Wenxiu Han1, Haixia Zhang2, Xiaoxue Gong1, Yujin Guo1, Mengqi Yang1, Hailiang Zhang1, Xueyuan Zhou2,  Gongying Li3, Yuanyuan Liu4,  Pei Jiang1 and Genquan Yan5*
  • 1Institute of Clinical Pharmacy and Pharmacology, Jining First People's Hospital, China
  • 2Jining First People's Hospital, China
  • 3Mental Health Institute, Jining Medical College, China
  • 4Research Center of Basic Medical Sciences, Tianjin Medical University, China
  • 5Department of Pharmacy, Shandong Provincial Hospital, China

There is a strong link between heart disease and depression, both of which are closely related to life time stress exposure. Serum and glucocorticoid regulated kinase 1 (SGK1) is a stress-responsive gene with a pivotal role in both heart and brain. To determine the role of SGK1 polymorphisms (rs2758151, rs1743963, rs9493857, rs1763509, rs9376026, 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, 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 PHQ-9 scores in the carriers of the risk genotype for comorbid depression, AA, were significantly higher than 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% 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 no significant differences were found for other SGK1 SNPs (rs2758151, rs9493857, rs9376026, 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.

Keywords: serum/glucocorticoid regulated kinase 1, coronary heart disease, Depression, polymorphism, stress

Received: 25 Jul 2018; Accepted: 30 Aug 2019.

Copyright: © 2019 Han, Zhang, Gong, Guo, Yang, Zhang, Zhou, Li, Liu, Jiang and Yan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Genquan Yan, Department of Pharmacy, Shandong Provincial Hospital, Jinan, Shandong Province, China, yangenquan@126.com