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Plasminogen activator inhibitor-1 4G/5G polymorphism is associated with coronary artery disease risk: a meta-analysis
Huifeng Zhang1, Pingshuan Dong1, Xuming Yang1
1Department of Cardiology, First Affiliated Hospital of Henan University of Science and Technology Luoyang 471003, Henan Province, China.
Insights
The Plasminogen activator inhibitor-1 (PAI-1) 4G/5G gene polymorphism is a significant risk factor for coronary artery disease (CAD). This finding was consistent across various populations and subgroups, including those with myocardial infarction and type 2 diabetes.
Area of Science:
- Genetics
- Cardiology
- Molecular Biology
Background:
- Coronary artery disease (CAD) is a leading cause of mortality worldwide.
- Genetic factors play a crucial role in the development of CAD.
- The Plasminogen activator inhibitor-1 (PAI-1) gene polymorphism, specifically the 4G/5G variant, has been implicated in cardiovascular disease risk.
Purpose of the Study:
- To conduct a comprehensive meta-analysis evaluating the association between the PAI-1 4G/5G polymorphism and the risk of developing coronary artery disease (CAD).
- To synthesize evidence from multiple studies to provide a robust estimate of the genetic risk conferred by this polymorphism.
Main Methods:
- Systematic literature search of major databases (PubMed, EMBASE, CNKI, etc.) up to June 2014.
- Inclusion of 72 studies comprising 23,557 cases and 21,526 controls.
- Statistical analysis using odds ratios (OR) and 95% confidence intervals (CI) to assess the association between PAI-1 4G/5G polymorphism and CAD risk.
Main Results:
- The PAI-1 4G/5G polymorphism was significantly associated with an increased risk of CAD in the overall population (OR=1.19).
- Significant associations were observed in Caucasians and Asians, as well as for myocardial infarction (MI) risk.
- The polymorphism was linked to increased risk in early-onset CAD, male patients, and individuals with type 2 diabetes mellitus (T2DM).
Conclusions:
- The PAI-1 4G/5G polymorphism is a confirmed risk factor for coronary artery disease.
- This genetic variant contributes to CAD susceptibility across diverse ethnic groups and clinical presentations.
- Further research may explore targeted interventions based on genetic predisposition.
Background:
The aim of the current study was to evaluate the association of PAI-1 4G/5G polymorphism with coronary artery disease (CAD) risk using a meta-analysis.
Methods:
All eligible studies were identified through a search of PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), Database of Chinese Scientific and Technical Periodicals, and China Biology Medical literature database (CBM) before June 2014. The association between the PAI-1 4G/5G polymorphism and CAD risk was estimated by odds ratio (OR) and 95% confidence interval (CI).
Results:
A total of 72 studies including 23557 cases and 21526 controls were eventually collected. The PAI-1 4G/5G polymorphism was significant associated with CAD risk in overall population (OR=1.19, 95% CI 1.10-1.28, P < 0.00001). The combination of adjusted ORs for CAD was 1.20 (95% CI 1.03-1.40, P=0.02). This polymorphism was associated with CAD risk in Caucasians (OR=1.10, 95% CI 1.02-1.19, P=0.01) and Asians (OR=1.46, 95% CI 1.21-1.75, P < 0.0001). This polymorphism significantly increased MI risk (OR=1.15, 95% CI 1.06-1.25, P=0.001). In the subgroup analysis by age, this polymorphism was significantly associated with early-onset CAD risk (OR=1.21, 95% CI 1.02-1.43, P=0.03). In the gender subgroup analyses, a statistically significant association was found in male CAD patients (OR=1.10, 95% CI 1.01-1.20, P=0.04). Both T2DM patients and non-T2DM patients carrying 4G allele showed increased CAD risks (OR=2.23, 95% CI 1.27-3.92, P=0.005 and OR=1.64, 95% CI 1.19-2.25, P=0.002, respectively).
Conclusions:
This meta-analysis suggested that PAI-1 4G/5G polymorphism was a risk factor for CAD.
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