Association of angiotensinogen m235t and a(-6)g gene polymorphisms with coronary heart disease with independence of essential hypertension: the procagene study

Abstract

This study shows that genetic variation of the AGT (M235T), but not the ACE (I/D), genotypes contributes to the presence of CHD independently of blood pressure profile in a subset of the Spanish population with a high prevalence of cardiovascular disease.

Polymorphisms of the Renin-Angiotensin System Genes Predict Progression of Subclinical Coronary Atherosclerosis

“…This additive effect of ACE ID heterozygote (but not ACE DD homozygote) seems rather surprising, and we cannot exclude possibilities of by chance association. Interestingly, the same interaction between AGT TT and ACE ID genotypes has been previously observed among nondiabetic patients with clinically diagnosed CAD (37). These findings are in line with the growing evidence that phenotypic effects of one locus could be altered or masked by effects of genetic variants of other loci that encode proteins involved in the same biochemical pathway (16,48).…”

“…Among type 1 diabetic patients, prevalence of coronary calcification was higher among hypertensive versus normotensive subjects (50.6 vs. 27.6%, P Ͻ 0.0001) and in those with albuminuria compared with patients free of albuminuria (57.5 vs. 34.5%, P Ͻ 0.0001). Given the facts that genetic variants of RAS have been associated with diabetic nephropathy/albuminuria (35)(36)(37)(38) and/or hypertension (13,16,28) and that both nephropathy and hypertension are the key risk factors for CAD and CAC development, type 1 diabetic patients were stratified by hypertension/albuminuria status to reveal a potential confounder effect of hypertension/albuminuria on RAS gene association with CAC progression ( Table 2). The prevalence of CAC was higher in subjects carrying the AGT 235TT genotype, compared with those with MT or MM genotypes among subjects without albuminuria and/or hypertension (respectively, 36 vs. 21.2 vs. 33.3%, P ϭ 0.048) but not among type 1 diabetic subjects with albuminuria and/or hypertension at the baseline visit (50 vs. 53.6 vs. 47.2%, P ϭ 0.65) or in healthy control subjects (21.4 vs. 25.8 vs. 31.4%, P ϭ 0.15).…”

Genetic Variation of the Renin-Angiotensin System and Chronic Kidney Disease Progression in Black Individuals in the Atherosclerosis Risk in Communities Study

“…Compared with the ancestral A(Ϫ6) allele, carriers of G(Ϫ6) may have lower risk, consistent with effects of this promoter polymorphism on a lower rate of transcription in vitro and of decreased cardiovascular disease risk (8,14). Consistent with its effects on modulating AGT transcription and renal remodeling (6,7,13), it may play a BP-independent role in CKD progression, with G(Ϫ6) carriers having a RR of CKD progression of 0.75 (95% CI 0.57 to 0.98).…”

“…However, the association of AGT and CKD progression was independent of BP in our study. Risk associations of AGT G(Ϫ6)A and CHD were similar in magnitude and also independent of hypertension (14).…”

“…Ang II regulates both BP and fibrosis (6), and in animal models, increased levels contribute to glomerulosclerosis and extracellular matrix (ECM) synthesis through induction of TGF-␤ (7,13). Compared with the A(Ϫ6) allele, the G(Ϫ6) variant of AGT has been shown to be protective for coronary heart disease (CHD) (14). The AGT M235T polymorphism has been associated with ESRD (15), but there has been no study of the tightly linked G(Ϫ6)A functional polymorphism and CKD.…”