Previous association studies between angiotensin-converting enzyme (ACE) and angiotensinogen (AGT) polymorphisms and several cardiovascular diseases have reported variable results.
To assess the value of genotyping AGT in a genetically homogeneous population, we carried out a retrospective, case control study of variants M235T and T174M for putative correlations with CVDs among nationals from the United Arab Emirates (Emirati)--an ethnic group characterized by no alcohol intake and no cigarette smoking.
We found no evidence that the ACE I/D and AGT T235 polymorphisms of the renin-angiotensin system were associated with carotid intima-media thickness in this population-based sample of middle-aged adults with no history of cardiovascular disease.
The significant relations observed between the AGTM235T variant, its protein product, and the cardiovascular disease phenotypes provide evidence for a possible role of elevated circulating AGT in the pathogenesis of coronary artery disease.
Several polymorphisms of genes encoding for components of the renin angiotensin system such as the M235T polymorphism in the angiotensinogen gene, the 287-base-pair insertion (I)/deletion (D) polymorphism at intron 16 of the ACE gene, and the A1166C polymorphism in the angiotensin II type 1 receptor gene have been associated with an increased risk of cardiovascular diseases.
Several studies based on different populations worldwide have described an association between cardiovascular diseases and genetic variations in the apolipoprotein E (A:POE), angiotensinogen (A:GT), angiotensin receptor type 1 (A:T1R), and angiotensin-converting enzyme (A:CE) genes.
Several other gene polymorphisms, in particular those in the promoter area of the angiotensinogen gene, have been studied in relation to cardiovascular disease.
The D-allele of ACE and T-allele of ATG gene exert a synergistic effect on cardiac hypertrophy in male patients with cardiovascular diseases, but not in normal healthy population.
Several genes that encode proteins involved in the maintenance of vascular tone, such as the endothelial-constitutive nitric oxide synthase (ecNOS), the angiotensinogen (AGT), the angiotensin-converting enzyme (ACE), and the angiotensin II receptor type 1 (AT1R) are polymorphic, and these polymorphisms have been associated with several cardiovascular diseases.
In addition, experimental evidence was presented that genetic manipulation of peptide systems (i.e., the renin-angiotensin II system and the kallikrein-kinin system) was effective in the treatment of systemic cardiovascular diseases such as hypertension, heart failure, and renal failure.
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.
The angiotensin II type 2 (AT2) receptor is thought to play a role in cardiovascular disorders such as neointima formation after vascular injury, cardiac hypertrophy and myocardial infarction (MI).
Polymorphism of the promoter region of the angiotensinogen gene (ATG) and an angiotensin I-converting enzyme gene (ACE) insertion/deletion (I/D) polymorphism were studied in three different groups of Kazakhs (control group, patients with cardiovascular disease (CAD) and patients with arterial hypertension (AH)) using three methods.
Renin-angiotensin systems may mediate cardiovascular disease pathogenesis through a balance of actions of angiotensin II on (potentially proatherogenic) constitutive type 1 (AT1R) and (potentially antiatherogenic) inducible type 2 (AT2R) receptors.
This review addresses several of the unanswered questions with regard to tissue angiotensin II generation, focussing in particular on the heart and vascular wall: (1) what is the origin of the renin that is required to generate angiotensin II locally, (2) where does tissue angiotensin generation occur (intra- versus extracellular), (3) what is the importance of alternative (non-renin, non-ACE) angiotensin-generating enzymes, (4) do ACE inhibitors and AT(1) receptor antagonists exert local effects that are renin-angiotensin system independent (thereby incorrectly leading to the conclusion that they interfere with the local generation or effects of angiotensin II), and (5) to what degree do differences in tissue angiotensin generation underlie the association between cardiovascular diseases and renin-angiotensin system gene polymorphisms?
The insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE), the A1166C polymorphism in the angiotensin type 1 receptor (AT1R), and the M235T polymorphism of the angiotensinogen gene are associated with cardiovascular disease mostly in men.
Moreover, to detect any relationship between AGTM235T variation and intermediate and quantitative traits relevant to the pathogenesis of cardiovascular disease and PCOS, we looked for genotype-dependent differences within the subjects with PCOS.