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      A Systematic Meta-Analysis of Genetic Association Studies for Diabetic Retinopathy

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          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.


          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.


          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 micro satellite was found to confer risk (OR 2.33 [95% CI 1.49–3.64], P = 2 × 10 −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 = 1.00 × 10 −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.


          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.

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          Most cited references 36

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                Author and article information

                American Diabetes Association
                September 2009
                8 July 2009
                : 58
                : 9
                : 2137-2147
                1Department of Ophthalmology, Flinders Medical Centre and Flinders University, Bedford Park, SA, Australia;
                2Centre for Eye Research Australia, Melbourne University, Melbourne, Victoria, Australia.
                Author notes
                Corresponding author: Jamie Craig, jamie.craig@ 123456flinders.edu.au .
                © 2009 by the American Diabetes Association.

                Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

                Original Article

                Endocrinology & Diabetes


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