Association analysis of genes in the renin-angiotensin system with subclinical cardiovascular disease in families with Type 2 diabetes mellitus: the Diabetes Heart Study.
OBJECTIVE
Cardiovascular disease (CVD) is a major complication of Type 2 diabetes mellitus. The renin-angiotensin system (RAS) and nitric oxide production are both important regulators of vascular function and blood pressure. Genes encoding proteins involved in these pathways are candidates for a contribution to CVD in diabetic patients. We have investigated variants of the angiotensinogen (AGT), angiotensin converting enzyme (ACE), angiotensin type 1 receptor (AT1R) and endothelial nitric oxide synthase (NOS3) genes for association with subclinical measures of CVD in families with Type 2 diabetes mellitus (T2DM).


METHODS
Atherosclerosis was measured by carotid intima-media thickness and calcification of the carotid and coronary arteries in 620 European Americans and 117 African Americans in the Diabetes Heart Study. Because of the role of these systems in blood pressure regulation, blood pressure was also investigated.


RESULTS
Compelling evidence of association was not detected with any of the SNPs with any outcome measures after adjustments for covariates despite sufficient power to detect relatively small differences in traits for specific genotype combinations.


CONCLUSIONS
Genetic variation of the RAS and NOS3 genes do not appear to strongly influence subclinical cardiovascular disease or blood pressure in this diabetic population.
Burdon
K P
KP
Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Langefeld
C D
CD
Wagenknecht
L E
LE
Carr
J J
JJ
Freedman
B I
BI
Herrington
D
D
Bowden
D W
DW
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000808:Angiotensinogen / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000503:physiopathology; D002318:Cardiovascular Diseases / Q000235:genetics* / Q000503:physiopathology; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000235:genetics*; D004727:Endothelium / Q000201:enzymology; D005192:Family Health; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000235:genetics; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics*; D012307:Risk Factors
D044140:Receptor, Angiotensin, Type 1; D000808:Angiotensinogen; D019001:Nitric Oxide Synthase; D007703:Peptidyl-Dipeptidase A