Dataset Information

The C825T Polymorphism of the G-Protein ?3 Gene as a Risk Factor for Depression: A Meta-Analysis.

ABSTRACT:

Background

TheG-protein ?3 gene (GN?3) has been implicated in psychiatric illness through its effects upon intracellular transduction of several neurotransmitter receptors. Multiple studies have investigated the relationship of the C825T polymorphism of the GN?3 gene (GN?3 C825T) to depression and antidepressant response. However, the relationship between GN?3 C825T and depression remains inconsistent. Therefore, here we performed a meta-analysis to investigate the role of GN?3 C825Tin depression risk.

Methods

Published case-control studies examining the association between GN?3 C825T and depression were systematically searched for through several electronic databases (PubMed, Scopus, Science Direct, Springer, Embase, psyINFO, and CNKI). The association between GN?3 C825T and depression risk were assessed by odd ratios (ORs) and their 95% confidence intervals (CIs) for each study. Pooled ORs were constructed for allele contrast (C versus T), homozygote (CC versus TT) model, heterozygote (CC versus CT) model, dominant model (CC + CT versus TT), and recessive (CC versus TT+CT) model. In order to evaluate possible biases, a sensitivity analysis was conducted by sequential deletion of individual studies in an attempt to assess the contribution of each individual dataset to the pooled OR.

Results

Nine studies, including 1055 depressed patients and 1325 healthy controls, were included. A significant association between GN?3 C825Tand depression was found to exist, suggesting that the T-allele of GN?3 C825Tcan increase susceptibility to depression. After stratification by ethnicity, the same association was found in the Asian subpopulation, but not the Caucasian subpopulation.

Conclusions

This is the first meta-analysis to reveal a relationship between GN?3 C825T and depression. Asian T-allele carriers of GN?3 C825T appear to be more susceptible to depression.

SUBMITTER: Fang L

PROVIDER: S-EPMC4493085 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

The C825T Polymorphism of the G-Protein β3 Gene as a Risk Factor for Depression: A Meta-Analysis.

Fang Liang L Zhou Chanjuan C Bai Shunjie S Huang Chenglong C Pan Junxi J Wang Ling L Wang Xinfa X Mao Qiang Q Sun Lu L Xie Peng P

PloS one 20150706 7

<h4>Background</h4>TheG-protein β3 gene (GNβ3) has been implicated in psychiatric illness through its effects upon intracellular transduction of several neurotransmitter receptors. Multiple studies have investigated the relationship of the C825T polymorphism of the GNβ3 gene (GNβ3 C825T) to depression and antidepressant response. However, the relationship between GNβ3 C825T and depression remains inconsistent. Therefore, here we performed a meta-analysis to investigate the role of GNβ3 C825Tin d ...[more]

PMID: 26147511

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Project description:ObjectiveSeveral epidemiological studies have evaluated the association between the GNB3 C825T polymorphism and hypertension or stroke. The results of these studies were inconsistent; therefore, we performed a meta-analysis to clarify these discrepancies.MethodsWe systematically searched the PubMed, Embase, Web of Science, CNKI, and CBM databases, and manually searched reference lists of relevant papers, meeting abstracts, and relevant journals. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for dominant, recessive, and allelic models. A fixed or random effects model was separately adopted depending on study heterogeneity. Subgroup and sensitivity analyses were performed to detect study heterogeneity and examine result stability, respectively. Publication bias was tested using funnel plots, the Egger's regression test, and Begg's test.ResultsWe screened 66 studies regarding hypertension and eight concerning stroke. A combined analysis showed that only the allelic model found a marginal association with hypertension (OR = 1.07, 95% CI = 1.01-1.13) and female gender (OR = 1.11, 95% CI = 0.99-1.24). However, no comparison models found an association with stroke (allelic model: OR = 1.11, 95% CI = 0.94-1.32; dominant model: OR = 1.16, 95% CI = 0.92-1.48; and recessive model: OR = 1.05, 95% CI = 0.97-1.14). Sensitivity analysis suggested that all models did not yield a relationship to hypertension or stroke among Asians. Besides, there was a lack of statistical association with hypertension in Caucasians, which maybe due to a small sample size. When we restricted the included studies to normal populations according to the Hardy-Weinberg equilibrium, no association was found.ConclusionsThere was no evidence indicating that the 825T allele or TT genotype was associated with hypertension or stroke in Asians or hypertension in Caucasians. However, further studies regarding Africans and other ethnicities are needed to identify further correlations.

Project description:The GNB3 C825T polymorphism is associated with increased G protein-mediated signal transduction, SDF-1?-mediated lymphocyte chemotaxis, accelerated HIV-1 progression, and altered responses to antiretroviral therapy among Caucasian subjects. The GNB3 825T allele is highly prevalent in African populations, and as such any impact on HIV-1 acquisition or progression rates could have a dramatic impact. This study examines the association of the 825T polymorphism with HIV-1 acquisition, disease progression and immune activation in two African cohorts. GNB3 825 genotyping was performed for enrolees in both a commercial sex worker cohort and a perinatal HIV transmission (PHT) cohort in Nairobi, Kenya. Ex vivo immune activation was quantified by flow cytometry, and plasma chemokine levels were assessed by cytokine bead array.GNB3 genotype was not associated with sexual or vertical HIV-1 acquisition within these cohorts. Within the Pumwani cohort, GNB3 genotype did not affect HIV-1 disease progression among seroconverters or among HIV-1-positive individuals after adjustment for baseline CD4 count. Maternal CD4 decline and viral load increase in the PHT cohort did not differ between genotypes. Multi-parametric flow cytometry assessment of T cell activation (CD69, HLA-DR, CD38) and Treg frequency (CD25(+)FOXP3(+)) found no differences between genotype groups. Plasma SDF-1?, MIP-1? and TRAIL levels quantified by cytokine bead array were also similar between groups.In contrast to previous reports, we were unable to provide evidence to suggest that the GNB3 C825T polymorphism affects HIV-1 acquisition or disease progression within African populations. Ex vivo immune activation and plasma chemokine levels were similarly unaffected by GNB3 genotype in both HIV-1-negative and HIV-1-positive individuals. The paucity of studies investigating the impact of GNB3 polymorphism among African populations and the lack of mechanistic studies make it difficult to assess the true biological significance of this polymorphism in HIV-1 infection.