Dataset Information

Heterogeneous effect of two selectin gene polymorphisms on coronary artery disease risk: a meta-analysis.

ABSTRACT:

Background

The selectins play important roles in the inflammatory process of coronary artery disease (CAD) and myocardial infarction (MI). Previous studies have shown ambiguous findings regarding a possible association between the selectin genes and CAD. The E-selectin Ser128Arg polymorphism and the P-selectin Thr715Pro polymorphism have been investigated widely but with inconsistent results. We performed a comprehensive meta-analysis to shed light on this issue.

Methods

Data were extracted by searches of MEDLINE, Embase, CNKI, Wanfang, Google Scholar, PORTA, GeNii, CiNii, J-STAGE, Nurimedia and Koreanstudies Information Service System [Kiss] up to October 2013, in which 10 studies on the Ser128Arg polymorphism with 3369 cases and 2577 controls and 10 studies on the Thr715Pro polymorphism with 5886 cases and 18345 controls. A random-effects model was used to calculate the combined odds ratios. The between-study heterogeneity and publication bias were addressed.

Results

The 128Arg carriers had a significant increased risk of CAD (allele comparison: P?=?0.02, OR?=?1.33, 95%CI 1.04-1.69, P(heterogeneity)?=?0.01); The 715Pro conferred a non-significant risk reduction relative to the 715Thr (allele comparison: P?=?0.40, OR?=?0.94, 95%CI 0.82-1.08, P(heterogeneity)?=?0.03).Subgroup analyses demonstrated that the 128Arg carriers had a significant increased risk of CAD among Asians (allele comparison: P?=?0.001, OR?=?2.07, 95%CI 1.33-3.24, P(heterogeneity)?=?0.77) but not among Caucasians (allele comparison: P?=?0.33, OR?=?1.13, 95%CI 0.88-1.45, P(heterogeneity)?=?0.08). Carrier status for the 715Pro was significantly associated with reduced risk of MI (allele comparison: P?=?0.04, OR?=? 0.81, 95%CI 0.67-0.99, P(heterogeneity?)=?0.14). The asymmetric funnel plot and the Egger's test (P?=?0.041) suggested the presence of publication bias for the Ser128Arg polymorphism.

Conclusion

Our results suggested there is an increase in the risk of CAD conferred by the Ser128Arg polymorphism and the thr715Pro polymorphism may be a protective factor of MI.

SUBMITTER: Wu Z

PROVIDER: S-EPMC3912165 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Heterogeneous effect of two selectin gene polymorphisms on coronary artery disease risk: a meta-analysis.

Wu Zhijun Z Lou Yuqing Y Lu Lin L Liu Yan Y Chen Qiujing Q Chen Xin X Jin Wei W

PloS one 20140203 2

<h4>Background</h4>The selectins play important roles in the inflammatory process of coronary artery disease (CAD) and myocardial infarction (MI). Previous studies have shown ambiguous findings regarding a possible association between the selectin genes and CAD. The E-selectin Ser128Arg polymorphism and the P-selectin Thr715Pro polymorphism have been investigated widely but with inconsistent results. We performed a comprehensive meta-analysis to shed light on this issue.<h4>Methods</h4>Data were ...[more]

PMID: 24498435

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Project description:ObjectiveE-selectin (SELE) mediates the rolling and adhesion of leukocytes on activated endothelial cells and plays a critial role in the pathogenesis of coronary artery disease (CAD). Associatons between the A561C and G98T polymorphisms of the SELE gene and CAD risk were investigated broadly, but the results were inconsistent. In the present study, we performed a meta-analysis to systematically evaluate the associations between the two polymorphisms and the risk of CAD.MethodsComprehensive research was conducted to identify relevant studies. The fixed or random effect model was selected based on the heterogeneity among studies, which was evaluated with Q-test and ?(2). Meta-regression was used to explore the potential sources of between-study heterogeneity. Peters's linear regression test was used to estimate the publication bias.ResultsOverall, 24 articles involving 3694 cases and 3469 controls were included. After excluding articles deviating from Hardy-Weinberg equilibrium in controls and sensitive analysis, our meta-analysis showed a significant association between the A561C ploymprphism and CAD in dominant (OR=?1.84, 95% CI?=?1.56-2.16) and codominant (OR=?1.74, 95% CI=?1.49-2.03) models. As for the G98T polymorphism, significantly increased CAD risk was observed in dominant (OR?=?1.47, 95% CI=?1.16-1.87) and codominant (OR=?1.48, 95% CI?=?1.18-1.86) models, but after subgroup analysis, the association was not significant among Caucasians in dominant (OR=?1.58, 95% CI=?0.73-3.41) and codominant (OR=?1.58, 95% CI=?0.79-3.20) models.ConclusionsDespite some limitations, our meta-analysis suggested that the SELE gene polymorphisms (A561C, G98T) were significantly associated with increased risk of CAD. However, after subgroup analysis no significant association was found among Caucasians for the G98T polymorphism, which may be due to the small sample size and other confounding factors. Future investigations with multicenter, large-scale, and multi-ethnic groups are needed.

Project description:Genetic variations that influence DNA repair efficiency may contribute to coronary artery disease (CAD) susceptibility. Previous studies have investigated whether there was evidence of an association between polymorphisms at the X-ray repair cross complementing 1 (XRCC1) gene and susceptibility to CAD, but findings have been inconclusive. We identified eligible studies through a comprehensive literature search to determine whether an association exists between XRCC1 gene polymorphisms and CAD susceptibility. Findings were assessed using the odds ratio (OR) and corresponding 95% confidence interval (CI), which were calculated using a fixed- or random-effects model, based on the heterogeneity of the studies. Ten eligible studies were finally included in this meta-analysis. Our pooled analysis found that XRCC1 polymorphisms were significantly associated with CAD susceptibility under recessive (Arg194Trp: OR = 1.47, 95% CI = 1.13-1.93; Arg399Gln: OR = 1.45, 95% CI = 1.12-1.89), homozygous (Arg194Trp: OR = 1.37, 95% CI = 1.03-1.81; Arg399Gln: OR = 1.56, 95% CI = 1.19-2.05), and allele (Arg399Gln: OR = 1.18, 95% CI = 1.06-1.32) genetic models. Following subgroup analysis by ethnicity, in Asian populations, we found evidence of associations between the XRCC1 Arg194Trp polymorphism and CAD under recessive and homozygous genetic models, and between the XRCC1 Arg399Gln polymorphism and CAD under recessive, homozygous, and allele genetic models. Subgroup analysis stratified by control source revealed associations between the Arg194Trp and Arg399Gln polymorphisms and susceptibility to CAD under recessive and homozygous modes of inheritance, respectively. In addition, subgroup analysis stratified by sample size found that findings of the Arg194Trp polymorphism in large sample sizes were comparable to those found using pooled eligible studies. Based on our meta-analysis, we concluded that the XRCC1 gene polymorphisms, Arg194Trp and Arg399Gln, are associated with CAD susceptibility, specifically in Asian populations. However, additional, comprehensive and well-designed studies are warranted to confirm these findings.

Dataset Information

Heterogeneous effect of two selectin gene polymorphisms on coronary artery disease risk: a meta-analysis.

Background

Methods

Results

Conclusion

Publications

Heterogeneous effect of two selectin gene polymorphisms on coronary artery disease risk: a meta-analysis.

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