Abstract

Objective: Diabetic retinopathy (DR) is a sight threatening microvascular complication of diabetes mellitus 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 DR.

Research design and methods: All studies investigating the association of genetic variants with the development of DR were identified in Pubmed and ISI Web of Knowledge. Crude odds ratios (OR) and 95% confidence intervals (CI) were calculated, for single nucleotide polymorphisms (SNPs) and microsatellite markers, previously investigated in at least 2 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 DR. The z-2 microsatellite 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 (OR: 0.58 95% CI: 0.36–0.93, p=0.02) against DR in type 2 diabetes regardless of ethnicity. The T allele of the AKR1B1 promoter rs759853 variant is also significantly protective against DR in type 1 diabetes (OR: 0.5, 95% CI: 0.35–0.71, p=1.00×10⁻⁴), regardless of ethnicity. These associations were also found in the Caucasian population alone (p<0.05). Polymorphisms in NOS3, VEGF, ITGA2 and ICAM1 are also associated with DR after meta-analysis.

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