Polymorphisms of the renin-angiotensin system genes predict progression of subclinical coronary atherosclerosis.
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.
Kretowski
Adam
A
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, USA. adam.kretowski@UCHSC.edu
McFann
Kim
K
Hokanson
John E
JE
Maahs
David
D
Kinney
Gregory
G
Snell-Bergeon
Janet K
JK
Wadwa
R Paul
RP
Eckel
Robert H
RH
Ogden
Lorraine
L
Garg
Satish
S
Li
Jia
J
Cheng
Suzanne
S
Erlich
Henry A
HA
Rewers
Marian
M
D000328:Adult; D000809:Angiotensins / Q000235:genetics; D015415:Biomarkers; D003324:Coronary Artery Disease / Q000235:genetics / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics*; D012307:Risk Factors
D000809:Angiotensins; D015415:Biomarkers; D044140:Receptor, Angiotensin, Type 1; D007703:Peptidyl-Dipeptidase A