title: Angiotensin II type 1 receptor gene polymorphisms in patients with cardiac hypertrophy.
abstract: Chronic mechanical stress of the heart secondary to arterial hypertension is a primary cause of left ventricular hypertrophy (LVH). The renin-angiotensin system (RAS) plays an important role in the cardiovascular system, regulating the expression of cardiac hypertrophy, in part, independent of the effects of systemic hypertension. A major component of RAS is angiotensin converting enzyme (ACE), which is upregulated in pressure overload-induced cardiac hypertrophy as well as heart failure. In a recent study, we found that the T allele of the M235T polymorphism of the angiotensinogen gene in sporadic hypertrophic cardiomyopathy (HCM) patients is associated with LVH. The present study was designed to assess the contribution of the polymorphisms of the angiotensin II type 1 receptor (AGT1R A1166C) genes on development of left ventricular hypertrophy. Patients with hypertensive LVH and relatives of HCM without manifesting the disease, showed higher C allele frequency compared to patients with HCM (11.3% vs 4.2%, chi 2 = 5.3, p < 0.05 and 10.5% vs 4.2%, chi 2 = 5.3, p < 0.05, respectively), but healthy controls did not (11.3% vs 7.5%, chi 2 = 1.42, NS and 10.5% vs 7.5%, chi 2 = 1.2, NS). The strong interaction between ACE I/D and AGT1R A1166C gene polymorphisms has been found in groups of relatives of HCM patients; odds ratio associated with ACE D allele was significant in subjects carrying the AGT1R C allele (OR = 7.3, 95% CI 1.6-33.1; chi 2 = 7.9, p < 0.02) compared with healthy subjects. We conclude that the molecular variant of the AGT1R A1166C gene is not contributing to the development of cardiac hypertrophy in hypertensive LVH and HCM patients, whereas carriers of both C and D alleles had a four-fold increase in the odds ratio for family history of HCM without manifesting the disease.
authors.affiliation: Department of Cardiovascular Medicine, Hokkaido University, School of Medicine, Sapporo, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Ishanov
authors.forename: H
authors.initials: H
authors.lastname: Okamoto
authors.forename: M
authors.initials: M
authors.lastname: Watanabe
authors.forename: K
authors.initials: K
authors.lastname: Yoneya
authors.forename: I
authors.initials: I
authors.lastname: Nakagawa
authors.forename: H
authors.initials: H
authors.lastname: Kumamoto
authors.forename: S
authors.initials: S
authors.lastname: Chiba
authors.forename: A
authors.initials: A
authors.lastname: Hata
authors.forename: H
authors.initials: H
authors.lastname: Kawaguchi
authors.forename: A
authors.initials: A
authors.lastname: Kitabatake
mesh_terms: D000368:Aged; D006332:Cardiomegaly / Q000235:genetics* / Q000503:physiopathology; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics; D005260:Female; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000209:etiology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000502:physiology*; D011945:Receptors, Angiotensin / Q000235:genetics*; D012084:Renin-Angiotensin System / Q000502:physiology*
chemical_list: D011945:Receptors, Angiotensin