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Association of FKBP5 polymorphisms with patient susceptibility to coronary artery disease comorbid with depression.

ABSTRACT: Background:Coronary artery disease (CAD) and depression cause great burden to society and frequently co-occur. The exact mechanisms of this comorbidity are unclear. FK506-binding protein 51 (FKBP51) is correlated with cardiovascular disease and depression. The aim of this study was to determine the role of the seven single nucleotide polymorphisms (SNPs) of FKBP5 that code FKBP51, namely, rs1360780 (C>T), rs2817032 (T>C), rs2817035 (G>A), rs9296158 (G>A), rs9470079 (G>A), rs4713902 (T>C), and rs3800373 (C>T) in a patient's susceptibility to comorbid CAD and depression. Methods:We enrolled 271 Northern Chinese Han patients with CAD, including 123 patients with depression and 147 patients without depression. We also included 113 healthy controls that match the patients' sex and age. Genomic DNA from whole blood was extracted, and seven SNPs were assessed using MassArray method. Patient Health Questionnaire-9 was applied to access the depression. Results:The GA genotype for rs9470079 was associated with a significantly decreased risk of CAD (odds ratio = 0.506, 95% confidence interval = 0.316-0.810, P = 0.005) when the GG genotype was used as reference. A statistically significant difference was observed among females but not among males in the rs9470079 genotype and allele frequency. Patients with CAD were further divided into CAD+D and CAD-D groups according to the presence of comorbid depression and were compared with the controls. Significant differences were found regarding the genotype and allele frequency of rs2817035 and rs9470079 in CAD+H groups compared with the control subjects in all groups and the female groups (P < 0.05). Conclusions:The current study found a remarkable association between FKBP5 gene variations and the risk of comorbid CAD and depression in a north Chinese population. rs9470079 may be a potential gene locus for the incidence of comorbid CAD and depression.

SUBMITTER: Wang H

PROVIDER: S-EPMC7275678 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Association of FKBP5 polymorphisms with patient susceptibility to coronary artery disease comorbid with depression.

Wang Haidong H Wang Chao C Song Xingfa X Liu Hai H Zhang Yun Y Jiang Pei P

PeerJ 20200603

<h4>Background</h4>Coronary artery disease (CAD) and depression cause great burden to society and frequently co-occur. The exact mechanisms of this comorbidity are unclear. FK506-binding protein 51 (FKBP51) is correlated with cardiovascular disease and depression. The aim of this study was to determine the role of the seven single nucleotide polymorphisms (SNPs) of <i>FKBP5</i> that code FKBP51, namely, rs1360780 (C>T), rs2817032 (T>C), rs2817035 (G>A), rs9296158 (G>A), rs9470079 (G>A), rs471390 ...[more]

PMID: 32547886

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Project description: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.

Dataset Information

Association of FKBP5 polymorphisms with patient susceptibility to coronary artery disease comorbid with depression.

Publications

Association of FKBP5 polymorphisms with patient susceptibility to coronary artery disease comorbid with depression.

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