Functional polymorphisms in genes of the Angiotensin and Serotonin systems and risk of hypertrophic cardiomyopathy: AT1R as a potential modifier

Abstract

BackgroundAngiotensin and serotonin have been identified as inducers of cardiac hypertrophy. DNA polymorphisms at the genes encoding components of the angiotensin and serotonin systems have been associated with the risk of developing cardiovascular diseases, including left ventricular hypertrophy (LVH).MethodsWe genotyped five polymorphisms of the AGT, ACE, AT1R, 5-HT2A, and 5-HTT genes in 245 patients with Hypertrophic Cardiomyopathy (HCM; 205 without an identified sarcomeric gene mutation), in 145 patients with LVH secondary to hypertension, and 300 healthy controls.ResultsWe found a significantly higher frequency of AT1R 1166 C carriers (CC+AC) among the HCM patients without sarcomeric mutations compared to controls (p = 0.015; OR = 1.56; 95%CI = 1.09-2.23). The AT1R 1166 C was also more frequent among patients who had at least one affected relative, compared to sporadic cases. This allele was also associated with higher left ventricular wall thickness in both, HCM patients with and without sarcomeric mutations.ConclusionsThe 1166 C AT1R allele could be a risk factor for cardiac hypertrophy in patients without sarcomeric mutations. Other variants at the AGT, ACE, 5-HT2A and 5-HTT did not contribute to the risk of cardiac hypertrophy.

Myosin‐Binding Protein C DNA Variants in Domestic Cats (A31P, A74T, R820W) and their Association with Hypertrophic Cardiomyopathy

“…In humans, mutations in MYBPC3 typically exhibit low and age‐related penetrance in heterozygotes. A few modifying genes and their proteins have been identified that contribute to the penetrance of these mutations, including the angiotensin‐converting‐enzyme gene and the gene that encodes for the angiotensin1‐receptor . These and other “modifying” genes, suggested by the incomplete penetrance and phenotypic heterogeneity, have not been identified in cats.…”

“…A few modifying genes and their proteins have been identified that contribute to the penetrance of these mutations, including the angiotensin-converting-enzyme gene and the gene that encodes for the angiotensin1-receptor. 16 These and other "modifying" genes, suggested by the incomplete penetrance and phenotypic heterogeneity, have not been identified in cats. Furthermore, no other major HCM causative mutations in other feline breeds have been identified.…”

The Influence of Angiotensin Converting Enzyme and Angiotensinogen Gene Polymorphisms on Hypertrophic Cardiomyopathy

“…A total of seventeen studies were included in our review [1], [13], [20], [21], [23], [25], [26], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44]. For ACE I/D polymorphism, a total of 31 prospective trials surveyed the polymorphism of ACE I/D.…”

Impaired Endothelium Independent Vasodilation in Nonobstructive Hypertrophic Cardiomyopathy

“…13 Abnormalities in the renin-angiotensin system, namely specific polymorphisms in the angiotensin genes, have been suggested as potential candidate mechanisms capable to explain coexisting myocardial and vascular hypertrophy and fibrosis in HCM patients. 14 Recently, Boonyasirinant et al reported an increased aortic stiffness in patients with HCM, above all in those with myocardial fibrosis. 15 All these data imply that HCM, apart from being a cardiac disease, may also affect the vascular system, with structural changes of the arterial wall, rearrangement, and remodeling of its three-dimensional architecture limiting maximal vasodilator capacity.…”