Journal Article

Genetic polymorphisms of the renin–angiotensin system and complications of insulin‐dependent diabetes mellitus

Frans J. van Ittersum, Angelique M. E. de Man, Sandra Thijssen, Peter de Knijff, Eline Slagboom, Yvo Smulders, Lise Tarnow, Ab J. M. Donker, Henk J. G. Bilo and Coen D. A. Stehouwer

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 15, issue 7, pages 1000-1007
Published in print July 2000 | ISSN: 0931-0509
Published online July 2000 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/15.7.1000
Genetic polymorphisms of the renin–angiotensin system and complications of insulin‐dependent diabetes mellitus

Show Summary Details

Preview

Objective. Patients with insulin‐dependent diabetes mellitus (IDDM) have a high risk of developing diabetic nephropathy, retinopathy and cardiovascular diseases. The contribution of gene polymorphisms of the renin angiotensin system to these complications is controversial and may differ among populations.

Methods. In 257 Dutch IDDM patients (188 with urinary albumin excretion (UAE) <30 mg/24 h), logistic regression analysis was used to study the relationships among, on the one hand, the insertion/deletion gene polymorphism of the angiotensin‐converting enzyme gene (ACE‐ID), the M235T gene polymorphism of the angiotensinogen gene (AGT‐M235T), and the A1166C gene polymorphism of the angiotensin type 1 receptor gene (AT1‐A1166C), and, on the other hand, UAE, retinopathy, hypertension, and coronary heart disease.

Results. The T‐allele of the AGT‐M235T polymorphism was associated with an increased risk of an elevated UAE (odds ratio (OR) 3.03; 95% confidence interval (CI) 1.06–8.61), but only when interaction with the D‐allele of the ACE‐ID polymorphism was considered. A previously described positive interaction between the T‐allele of the AGT‐M235T polymorphism and the D‐allele of the ACE‐ID polymorphism could not be confirmed. The T‐allele was also associated with an increased risk of retinopathy (OR 3.89, 95% CI 1.79–8.47). The CC‐genotype of the AT1‐A1166C polymorphism was associated with hypertension (OR 3.58; 95% CI 1.23–10.37).

Conclusions. In a Dutch IDDM population, including 69 patients with (incipient) diabetic nephropathy, the T‐allele of the AGT‐M235T polymorphism is associated with an elevated UAE and diabetic retinopathy and the CC‐genotype of the AT1‐A1166C polymorphism is associated with hypertension. A previously described interaction between the AGT‐M235T and the ACE‐ID polymorphisms could not be confirmed. Since the number of nephropathic patients in this study is small, these conclusions must be interpreted with caution.

Keywords: insulin‐dependent diabetes mellitus; complications; angiotensin‐converting enzyme gene polymorphism; angiotensinogen gene polymorphism; angiotensin II type 1 receptor gene polymorphism

Journal Article.  5296 words. 

Subjects: Nephrology

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.