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DOI: 10.2337/db06-1321
© 2007 by the American Diabetes Association
Polymorphisms of the Renin-Angiotensin System Genes Predict Progression of Subclinical Coronary Atherosclerosis
1 Barbara Davis Center for Childhood Diabetes, University of Colorado at Denver and Health Sciences Center, Aurora, Colorado
2 Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland
3 Department of Preventive Medicine and Biometrics, University of Colorado at Denver and Health Sciences Center, Denver, Colorado
4 Department of Medicine, University of Colorado at Denver and Health Sciences Center, Denver, Colorado
5 Human Genetics Department, Roche Molecular Systems, Alameda, California
Address correspondence and reprint requests to Adam Kretowski, MD, PhD, Barbara Davis Center for Childhood Diabetes, University of Colorado at Denver and Health Sciences Center, Mail Stop A140, P.O. Box 6511, Aurora, CO 80045-6511. E-mail: adam.kretowski{at}UCHSC.edu
Abbreviations:
ACEI, ACE inhibitor; AER, albumin excretion rate; AGT, angiotensinogen; ARB, angiotensin receptor blocker; ATR1, angiotensin type 1 receptor; CAC, coronary artery calcification; CAD, coronary artery disease; CRP, C reactive protein; CVS, calcium volume score; PAI-1, plasminogen activator inhibitor 1; RAS, renin-angiotensin system; SNP, single nucleotide polymorphism
Premature coronary artery disease (CAD) in subjects with type 1 diabetes dramatically affects quality of life and morbidity and leads to premature death, but there is still little known about the mechanisms and predictors of this complication. In the present study, we explored the role of genetic variants of angiotensinogen (AGT, M235T), ACE (I/D), and angiotensin type 1 receptor (ATR1, A1166C) as predictors of rapid progression of subclinical coronary atherosclerosis. Five-hundred eighty-five type 1 diabetic patients and 592 similar age and sex control subjects were evaluated for progression of coronary artery calcification (CAC), a marker of subclinical CAD, before and after a 2.5-year follow-up. In logistic regression analysis, CAC progression was dramatically more likely in type 1 diabetic subjects not treated with ACE inhibitor/angiotensin receptor blocker who had the TT-ID-AA/AC genotype combination than in those with other genotypes (odds ratio 11.6 [95%CI 4.5–29.6], P < 0.0001) and was even stronger when adjusted for cardiovascular disease risk factors and the mean A1C (37.5 [3.6–388], P = 0.002). In conclusion, a combination of genotype variants of the renin-angiotensin system genes is a powerful determinant of subclinical progression of coronary artery atherosclerosis in type 1 diabetic patients and may partially explain accelerated CAD in type 1 diabetes.
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 E. J. van Beers and M. C. Meuwese Comment on: Kretowski et al. (2007) Polymorphisms of the Renin-Angiotensin System Genes Predict Progression of Subclinical Coronary Atherosclerosis: Diabetes 56:863-871 Diabetes, July 1, 2007; 56(7): e5 - e5. [Full Text] [PDF]
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A. Kretowski and M. Rewers Response to Comment on: Kretowski et al. (2007) Polymorphisms of the Renin-Angiotensin System Genes Predict Progression of Subclinical Coronary Atherosclerosis: Diabetes 56:863-871 Diabetes, July 1, 2007; 56(7): e6 - e6. [Full Text] [PDF]
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