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A systematic meta-analysis of genetic association studies for diabetic retinopathy

Citation

Abhary, S and Hewitt, AW and Burdon, KP and Craig, JE, A systematic meta-analysis of genetic association studies for diabetic retinopathy, Diabetes, 58, (9) pp. 2137-2147. ISSN 0012-1797 (2009) [Refereed Article]


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Copyright Statement

Copyright2009 by the American Diabetes Association Licenced under Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported (CC BY-NC-ND 3.0) http://creativecommons.org/licenses/by-nc-nd/3.0/

Official URL: http://dx.doi.org/

DOI: doi:10.2337/db09-0059

Abstract

Objective: Diabetic retinopathy is a sight-threatening microvascular complication of diabetes with a complex multifactorial pathogenesis. A systematic meta-analysis was undertaken to collectively assess genetic studies and determine which previously investigated polymorphisms are associated with diabetic retinopathy.

Research Design and Methods: All studies investigating the association of genetic variants with the development of diabetic retinopathy were identified in PubMed and ISI Web of Knowledge. Crude odds ratios (ORs) and 95% CIs were calculated for single nucleotide polymorphisms and microsatellite markers previously investigated in at least two published studies.

Results: Twenty genes and 34 variants have previously been studied in multiple cohorts. The aldose reductase (AKR1B1) gene was found to have the largest number of polymorphisms significantly associated with diabetic retinopathy. The z-2 microsatellite was found to confer risk (OR 2.33 [95% CI 1.49 -3.64], P=2נ10-4) in type 1 and type 2 diabetes and z+2 to confer protection (0.58 [0.36-0.93], P = 0.02) against diabetic retinopathy in type 2 diabetes regardless of ethnicity. The T allele of the AKR1B1 promoter rs759853 variant is also significantly protective against diabetic retinopathy in type 1 diabetes (0.5 [0.35-0.71], P=1.00נ10-4), regardless of ethnicity. These associations were also found in the white population alone (P<0.05). Polymorphisms in NOS3, VEGF, ITGA2, and ICAM1 are also associated with diabetic retinopathy after meta-analysis.

Conclusions: Variations within the AKR1B1 gene are highly significantly associated with diabetic retinopathy development irrespective of ethnicity. Identification of genetic risk factors in diabetic retinopathy will assist in further understanding of this complex and debilitating diabetes complication.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Ophthalmology and Optometry
Research Field:Ophthalmology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Hearing, Vision, Speech and Their Disorders
Author:Hewitt, AW (Dr Alex Hewitt)
Author:Burdon, KP (Associate Professor Kathryn Burdon)
ID Code:91092
Year Published:2009
Web of Science® Times Cited:95
Deposited By:Menzies Institute for Medical Research
Deposited On:2014-05-07
Last Modified:2014-10-03
Downloads:213 View Download Statistics

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