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Plasminogen activator inhibitor-1 4G/5G polymorphism and retinopathy risk in type 2 diabetes: a meta-analysis
Open accessAbstract
Background: Mounting evidence has suggested that plasminogen activator inhibitor-1 (PAI-1) is a candidate for increased risk of diabetic retinopathy. Studies have reported that insertion/deletion polymorphism in the PAI-1 gene may influence the risk of this disease. To comprehensively address this issue, we performed a meta-analysis to evaluate the association of PAI-1 4G/5G polymorphism with diabetic retinopathy in type 2 diabetes. Methods: Data were retrieved in a systematic manner and analyzed using Review Manager and STATA Statistical Software. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. Results: Nine studies with 1, 217 cases and 1, 459 controls were included. Allelic and genotypic comparisons between cases and controls were evaluated. Overall analysis suggests a marginal association of the 4G/5G polymorphism with diabetic retinopathy (for 4G versus 5G: OR 1.13, 95%CI 1.01 to 1.26; for 4G/4G versus 5G/5G: OR 1.30, 95%CI 1.04 to 1.64; for 4G/4G versus 5G/5G + 4G/5G: OR 1.26, 95%CI 1.05 to 1.52). In subgroup analysis by ethnicity, we found an association among the Caucasian population (for 4G versus 5G: OR 1.14, 95% CI 1.00 to 1.30; for 4G/4G versus 5G/5G: OR 1.33, 95%CI 1.02 to 1.74; for 4G/4G versus 5G/5G + 4G/5G: OR 1.41, 95%CI 1.13 to 1.77). When stratified by the average duration of diabetes, patients with diabetes histories longer than 10 years have an elevated susceptibility to diabetic retinopathy than those with shorter histories (for 4G/4G versus 5G/5G: OR 1.47, 95%CI 1.08 to 2.00). We also detected a higher risk in hospital-based studies (for 4G/4G versus 5G/5G+4G/5G: OR 1.27, 95%CI 1.02 to 1.57). Conclusions: The present meta-analysis suggested that 4G/5G polymorphism in the PAI-1 gene potentially increased the risk of diabetic retinopathy in type 2 diabetes and showed a discrepancy in different ethnicities. A higher susceptibility in patients with longer duration of diabetes (more than 10 years) indicated a gene-environment interaction in determining the risk of diabetic retinopathy.
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Metadata
- Authors
- Zhang, T., Pang, C., Li, N., Zhou, E., & Zhao, K.
- Affiliations
- Tianjin Medical University (CN)
- Tianjin Medical University Cancer Institute and Hospital (CN)
- Tianjin Medical University Eye Hospital (CN)
- Yale University (US)
- Corresponding author
- Zhao, Kanxing
- Venue
- BMC Medicine
- Published
- 2013-01-02
- Volume
- 11
- Issue
- 1
- Pages
- 1-1
- ISSN
- 1741-7015 (ISSN-L)
- PMC
- PMC3565939
- OpenAlex
- W1978237749
- Cited by
- 270
- References
- 45
- Citations by year
- 2026: 6 · 2025: 24 · 2024: 21 · 2023: 18 · 2022: 28 · 2021: 37 · 2020: 11 · 2019: 15 · 2018: 17 · 2017: 30 · 2016: 30 · 2015: 19 · 2014: 10 · 2013: 4
- FWCI
- 3.67
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- BMC Medicine (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Tianjin Medical University
- Project 211
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- plasminogen activator inhibitor-1, PAI-1 4G/5G polymorphism, diabetic retinopathy, type 2 diabetes, genetic susceptibility, insertion/deletion polymorphism, diabetes duration, Caucasian population, ethnicity-stratified analysis, fibrinolysis, hypercoagulability, retinopathy risk factors, gene-environment interaction, alcohol consumption
- MeSH terms
- Diabetes Mellitus, Type 2, Diabetic Retinopathy, Ethnicity, Humans, Polymorphism, Genetic, Plasminogen Activator Inhibitor 1, Risk Assessment, Diabetes Complications
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