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Published online June 3, 2008
Diabetes 57:2541-2546, 2008
DOI: 10.2337/db08-0581
© 2008 by the American Diabetes Association
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Brief Report

Is the Presence of Retinopathy of Practical Value in Defining Cases of Diabetic Nephropathy in Genetic Association Studies?

The Experience With the ACE Insertion/Deletion Polymorphism in 53 Studies Comprising 17,791 Subjects

Daniel P.K. Ng, Bee-Choo Tai, and Xiu-Li Lim

From the Department of Community, Occupational and Family Medicine, National University of Singapore, Singapore

Corresponding author: Daniel P.K. Ng, cofnpkd{at}nus.edu.sg

OBJECTIVE— A key consideration when setting up genetic studies is the case definition. For diabetic nephropathy, the case definition is typically based on the presence of albuminuria. However, it has been long debated whether diabetic nephropathy cases defined in this way may have a high prevalence of nondiabetic kidney disease, especially if diabetic retinopathy is absent.

RESEARCH DESIGN AND METHODS— We performed a meta-analysis of 53 studies comprising 17,791 subjects investigating the angiotensin-I converting enzyme insertion/deletion polymorphism, taking into account the requirement for diabetic retinopathy in the case definition and assuming a random-effects model.

RESULTS— No publication bias was observed. The overall pooled odds ratio (OR) for all 53 studies was 0.78 (95% CI 0.70–0.87; P < 0.001), which indicated a significant protection against diabetic nephropathy for genotype II compared with carriage of the D-allele. The pooled OR for the 11 studies (n = 3,413) requiring diabetic retinopathy in the case definition was 0.68 (0.53–0.86; P = 0.002), and this was not significantly different from the pooled OR of 0.81 (0.71–0.92; P = 0.001) obtained from the 42 remaining studies (n = 14,378) (P = 0.198). This lack of any significant effect of diabetic retinopathy was reiterated in subgroup analyses based on the type of diabetes present.

CONCLUSIONS— Stipulating the presence of diabetic retinopathy in the case definition of diabetic nephropathy did not appear to confer tangible benefits when detecting genetic associations. Besides reducing sample sizes, this stipulation makes the interpretation of genetic associations more difficult due to the potential confounding presence of diabetic retinopathy.


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Copyright © 2008 by the American Diabetes Association.