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

被引:167
作者
Abhary, Sotoodeh [1 ,2 ]
Hewitt, Alex W. [1 ,2 ,3 ]
Burdon, Kathryn P. [1 ,2 ]
Craig, Jamie E. [1 ,2 ]
机构
[1] Flinders Med Ctr, Dept Ophthalmol, Bedford Pk, SA, Australia
[2] Flinders Univ S Australia, Bedford Pk, SA, Australia
[3] Univ Melbourne, Ctr Eye Res Australia, Melbourne, Vic, Australia
基金
英国医学研究理事会;
关键词
ENDOTHELIAL GROWTH-FACTOR; RENIN-ANGIOTENSIN SYSTEM; CONVERTING-ENZYME GENE; RETINAL MURAL CELLS; NITRIC-OXIDE; ALDOSE REDUCTASE; MICROVASCULAR COMPLICATIONS; CLINICAL-TRIALS; UNITED-STATES; POLYMORPHISM;
D O I
10.2337/db09-0059
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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% Cl 1.49-3.64], P = 2 X 10(-4)) in type I 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 x 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. 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. Diabetes 58:2137-2147, 2009
引用
收藏
页码:2137 / 2147
页数:11
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