Dataset Information

GNB3 and CREB1 gene polymorphisms combined with negative life events increase susceptibility to major depression in a Chinese Han population.

ABSTRACT:

Background

Major depression (MD) is caused by a combination of genetic and environmental factors. In this study we investigated the interaction of variations in the G-protein beta 3 subunit (GNB3) and cAMP response element binding protein 1 (CREB1) genes with negative life events in the pathogenesis of MD. One GNB3 polymorphism (rs5443) and four CREB1 polymorphisms (rs2253206, rs2551941, rs6740584, rs11904814) were investigated based on known associations with MD.

Methods

512 patients with MD and 513 control subjects were genotyped. The frequency and severity of negative life events were measured by the Life Events Scale (LES). Gene-environment interactions (G×E) were assessed using the generalized multifactor dimensionality reduction (GMDR) method.

Results

Differences in GNB3 rs5443 allele frequencies and genotype distributions were observed between MD patients and controls. Significant G×E interactions were detected between negative life events and genotypic variation of all five single nucleotide polymorphisms (SNPs). Individuals carrying the T- allele of rs5443 (CC), A- allele of rs2253206 (GG), T- allele of rs2551941 (AA), C- allele of rs6740584 (TT) or G- allele of rs11904814 (TT) conferred susceptibility to MD in subjects only exposed to high-negative life events. However, individuals with the T+ allele of rs5443 (CT, TT) were susceptible to MD when exposed to low negative life events.

Conclusions

Interactions between GNB3, CREB1 and negative life events were revealed. Further evidence is provided about the role of the environment in genetic vulnerability to MD.

SUBMITTER: Ma J

PROVIDER: S-EPMC5321408 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

GNB3 and CREB1 gene polymorphisms combined with negative life events increase susceptibility to major depression in a Chinese Han population.

Ma Jingsong J Wang Lin L Yang Yanjie Y Qiao Zhengxue Z Fang Deyu D Qiu Xiaohui X Yang Xiuxian X Zhu Xiongzhao X He Jincai J Pan Hui H Ban Bo B Zhao Yan Y Sui Hong H

PloS one 20170222 2

<h4>Background</h4>Major depression (MD) is caused by a combination of genetic and environmental factors. In this study we investigated the interaction of variations in the G-protein beta 3 subunit (GNB3) and cAMP response element binding protein 1 (CREB1) genes with negative life events in the pathogenesis of MD. One GNB3 polymorphism (rs5443) and four CREB1 polymorphisms (rs2253206, rs2551941, rs6740584, rs11904814) were investigated based on known associations with MD.<h4>Methods</h4>512 pati ...[more]

PMID: 28225778

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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.

Project description:BACKGROUND: Depression has been associated with chronic changes in the serum concentration of C-reactive protein (CRP) in observational studies, but it is unclear if this association is causal or is due to confounding and bias. Genetic studies are less subject to this type of error and offer an opportunity to investigate if CRP is causally linked to depression, particularly because known polymorphisms of the CRP gene have been associated with high- and low-basal serum concentrations of CRP [single nucleotide polymorphisms (SNPs) rs1130864 and rs1205, respectively]. The aim of this study is to determine if polymorphisms of SNPs rs1130864 and rs1205 are associated with prevalent depression. METHODS: We completed a cross-sectional study of a community sample of 3700 men aged > or = 70 years, and used the 15-item Geriatric Depression Scale (GDS-15) to assess depressive symptoms. A GDS-15 score 7 or more indicates the presence of clinically significant depressive symptoms. Physical morbidity was assessed with the physical component summary score (PCS) of the SF-36 Health Survey. We collected fasting blood samples to measure high sensitivity CRP and to extract DNA for the genotyping of SNPs rs1130864 and rs1205 of the CRP gene. RESULTS: One hundred and eighty-two men were depressed (4.9%). The odds of depression increased by 2% (95% CI = 1-4%) for every unit (mg/l) increase of CRP and nearly doubled for men with CRP > or = 3 mg/l vs <1 mg/l [odds ratio (OR) = 1.95, 95% confidence interval (CI) = 1.27-2.98]. However, the association between high CRP (> or = 3 mg/l) and depression was no longer significant after the analyses were adjusted for smoking, age, body mass index (BMI) and PCS. Men with the CT and TT genotypes of rs1130864 had 1.36 (95% CI = 1.13-1.63) and 2.31 (95% CI = 1.65-3.24) greater odds of CRP > or = 3 mg/l than CC carriers, but there was no association between this polymorphism and the presence of prevalent depression. The G > A polymorphism of SNP rs1205 was associated with 24% (95% CI = 16-32%) lower concentration of CRP compared with other genotypes. Men with the rs1205 AA genotype had 1.66 (95% CI = 1.07-2.57) and 1.67 (95% CI = 1.08-2.58) greater odds of having clinically significant depression than participants with the GA and GG genotypes, respectively. CONCLUSION: Our study shows that clinically significant depressive symptoms in later life are unlikely to be caused by an increase in the serum concentration of CRP. Instead, we found that the risk of depression was greater amongst people who carry the rs1205 G > A genetic polymorphism of the CRP gene, which was associated with approximately 20% lower serum concentration of CRP compared with other genotypes. This suggests that CRP may be a compensatory response to external insults that predispose to depression, and that an increase in the concentration of CRP might be adaptive.

Dataset Information

GNB3 and CREB1 gene polymorphisms combined with negative life events increase susceptibility to major depression in a Chinese Han population.

Background

Methods

Results

Conclusions

Publications

GNB3 and CREB1 gene polymorphisms combined with negative life events increase susceptibility to major depression in a Chinese Han population.

Similar Datasets

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