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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The review included a diverse range of literature, such as commentaries or theoretical papers which could contribute to programme theory development.
“Documents were selected for inclusion based on their relevance to the IPT and included a diverse range of literature, such as commentaries or theoretical papers which could contribute to programme theory development [36].”
From Do hospital-to-home transitions work for older adults with multiple long-term conditions including dementia? A realist review (2025) · cites this paper as [36]
The Methods (Search strategy) specify that eligible papers had to be case-control studies of the PAI-1 polymorphism and diabetic retinopathy, with genotype data sufficient to estimate an odds ratio. The Results (Eligible studies) report nine included case-control studies, contrary to the claim that this review included commentaries or theoretical papers for programme theory development. (LLM, conf=0.90)
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Experimental — accuracy not yet measuredQuality was assessed for relevance (contributed to IPT development/testing) and rigour (ensuring data were credible and trustworthy).
“Quality was assessment for relevance (i.e. contributed to IPT development/testing) and rigour (ensuring data were credible and trustworthy) [36].”
From Do hospital-to-home transitions work for older adults with multiple long-term conditions including dementia? A realist review (2025) · cites this paper as [36]
The Methods sections on Data extraction and Statistical analysis describe study selection and statistical checks for a meta-analysis of diabetic retinopathy; they do not describe assessing quality for relevance to IPT development or testing and rigour of data. Searches for those terms found no passage in our copy that addresses the claimed criteria. Page numbers were not available. (LLM, conf=0.76)
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- 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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