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.

Associations of FKBP5 polymorphisms and methylation and parenting style with depressive symptoms among Chinese adolescents

“…Similarly, Piechaczek et al reported that no main genetic effects of the five SNPs (rs3800373, rs9296158, rs1360780, rs9470080, and rs4713916) on depression were found [ 13 ]; Lou et al reported that rs7757037 of FKBP5 was associated with depression in Chinese systemic lupus erythematosus patients [ 40 ] in dominant model. However, this finding was inconsistent with a study among patients with coronary artery disease, indicating rs2817032 was not associated with depressive symptoms among those patients [ 41 ]. The diversity of populations, which might result in various gene sensitivity, may explain the discrepancy of genotype models, while this study focused on Chinese adolescents.…”

Associations of FKBP5 Polymorphisms and Methylation and Parenting Style With Depressive Symptoms Among Chinese Adolescents

“…Similarly, Piechaczek et al reported that no main genetic effects of the ve SNPs (rs3800373, rs9296158, rs1360780, rs9470080, and rs4713916) on depression were found [14]; Lou et al reported that rs7757037 of FKBP5 was associated with depression in Chinese systemic lupus erythematosus patients [34] in dominant model. However, this nding was inconsistent with a study among patients with coronary artery disease, indicating rs2817032 was not associated with depressive symptoms among those patients [35]. The diversity of populations, which might result in various gene sensitivity, may explain the discrepancy of genotype models, while this study focused on Chinese adolescents.…”

Association of SNPs in the FK-506 binding protein (FKBP5) gene among Han Chinese women with polycystic ovary syndrome

“…MAF of above all SNP were verified through 1000 Genomes CHB ( https://www.internationalgenome.org/ ), setting up cutoff MAF > 0.05. Among them, the SNPs rs2817035 and rs4713902 of the FKBP5 gene were reported as linked to risk for coronary artery disease [ 24 ]. A study of interindividual response differences to inhaled corticosteroids in patients with chronic obstructive pulmonary disease showed that rs4713916 is associated with sensitivity/resistance to corticosteroids [ 29 ].…”

“…Specifically, there is a distal enhancer located 65 kb downstream of the transcription start site in the fifth intron of the FKBP5 gene, and a study showed that FKBP5 expression is regulated by an interaction between the AR and this enhancer; specifically, AR selectively recruits cAMP response element-binding protein to this enhancer [ 22 ]. Moreover, it is notable that previous studies have shown that FKBP5 is highly expressed in muscle and adipose tissue, and human FKBP5 is associated with type 2 diabetes(T2D) and with markers for both insulin resistance and obesity [ 23 , 24 ]. Given that PCOS patients show symptoms like endocrine disorders, metabolic disorders, and obesity, we were interested in exploring potential relationships between FKBP5 and androgens in the context of PCOS etiology.…”