Hypertension Secondary To Left Ventricular Hypertrophy, Genetic Susceptibility And Hypertrophic Cardiomyopathy Of The Modified Gene

Background: Left ventricular hypertrophy (LVH) is associated with cardiovascular morbidity and mortality, as well as all-cause mortality. LVH is also independently associated with risk of ischemic stroke. Although hypertension is a major cause of LVH, the degree of LVH does not parallel to the level of blood pressure, the duration of hypertension, or reversal of hypertensive LVH by pharmacological treatments. This implies that other factors may be involved in LVH in addition to blood pressure. It has been reported that genetic factors account for 60% of blood pressure-independent cardiac mass variances. Experimental evidence supports a key role for beta(1)-adrenergic receptor (ADRB1) in the modulation of cardiac mass. This relationship has not yet been described in Chinese population.Objectives: We hypothesized that the polymorphisms of ADRB1 gene might confer higher risk of LVH. We tested whether the variations of ADRB1 gene Arg389Gly and Gly49Ser are associated with LVH in hypertensive patients.Methods: We tested our hypothesis in 2417 hypertensive patients which consisted of 1189 with LVH, 1228 without LVH. All subjects were genotyped for Arg389Gly and Gly49Ser polymorphisms.Results: Patients carrying the Arg389Arg genotype had increased left ventricular septal thickness (10.4±1.5mm vs 9.6±1.5mm,P<0.01 or 9.4±1.4mm,P<0.01, respectively); left ventricular posterior wall thickness (10.4±2.4mm vs 9.6±2.4 or 9.7±2.9mm, P<0.01, respectively); left ventricular mass index (51.6±13.3g/m²⁷ vs 44.6±12.9 g/m²⁷,P<0.01 or 43.2±14.4 g/m²⁷,P<0.01, respectively) and relative wall thicking (45.0±9.0% vs 42.6±8.1%, P<0.01 or 43.2±8.8%, P<0.01, respectively) as compared with the these carrying the genotypes Arg389Gly and Gly389Gly.These associations were independent of anthropometric factors and major clinical features and were confirmed in another hypertensive population (n=327).Conclusions: Our findings indicate that the Arg389Gly polymorphism of the ADRB1 gene might be a genetic risk factor for the development of LVH in patients with hypertension. Background: Hypertrophic cardiomyopathy (HCM) is a primary autosomal dominant inheritant myocardial disorder with heterogeneity in clinical manifestations, natural history and prognosis. Even carrying an identical gene mutation, inter-and intra-family variations have been noticed worldwide in the presence and the severity of left ventricular hypertrophy and sudden death in patients with HCM. Modifier genes may contribute to the diversity. Previous studies in vitro or in vivo have indicated that beta(1)-adrenergic receptor plays an important role in the progression of cardiac hypertrophy. Celiprolol, a selectiveβ1-bloker, can attenuate cadiac myocyte hypertrophy both in vitro and in vivo, these effects are mediated via the NO-signal pathway by stimulating the expression of endothelial NO synthase (eNOS). Studies also have proved that the eNOS plays a key role in the development of HCM. Our previous studies suggest that the polymorphisms of beta(1)-adrenergic receptor gene are associated with left ventricular hypertrophy in hypertension. The ADRB1 gene might be a modifier gene for the development of LVH in patients with HCM.Objectives:We tested whether SNPs in the ADRB1 gene associated with HCM.Methods:The hypothesis was tested in 267 patients with HCM and age-and sex-matched 816 healthy individuals. All subjects were genotyped for Arg389Gly and Gly49Ser polymorphisms.Results: No difference has been found in the frequency of the genotypes in the Arg389Gly and Gly49Ser polymorphisms of ADRB1 gene between patients with HCM and controls.Conclusions: The polymorphisms of ADRB1 gene were not associated with risk of HCM and other clinical phenotypes. The two variations of ADRB1 gene is not the genetic modifier for the development of HCM. Background: Left ventricular hypertrophy (LVH) is associated with cardiovascular morbidity and mortality, as well as all-cause mortality. LVH is also independently associated with risk of ischemic stroke. Although hypertension is a major cause of LVH, the degree of LVH does not parallel to the level of blood pressure, the duration of hypertension, or reversal of hypertensive LVH by pharmacological treatments. This implies that other factors may be involved in LVH in addition to blood pressure. It has been reported that genetic factors account for 60% of blood pressure-independent cardiac mass variances. Previous studies in vitro and vivo have proved that the stimulation of calcineurin can lead to cardic hypertrophy. The activity of calcineurin is regulated by many proteins such as cGMP-dependent protein kinaseâ… (PKGâ… ), heme oxygenase-1(HO-1), modulatory calcineurin-interacting protein 1(MCIP1) and glycogen synthase kinase 3 beta(GSK3β). Studies also have reported that PKGâ… ,HO-1,MCIP1 and GSK3βplay an important role in the progression of cardiac hypertrophy.We selected these genes as our candidate genes to study their association with LVH.Objectives: We hypothesized that polymorphisms of rs10995555,rs10822178 and rs4542348 of PKGâ… gene, rs2071747,rs17884059,rs17879895 and rs9282700 of HO-1 gene, rs8133540 of MCIP1 gene and rs334558,rs2276708å’Œrs3755557 of GSK3βgene may modify the diversity of LVH. To test our hypothesis, the associations of these polymorphisms with cardiac hypertrophy were tested in case-control studies.Methods: We tested our hypothesis in 2696 hypertensive patients consisted of 1271 with LVH, 1425 without LVH, and 720 healthy individuals as controls. All subjects were genotyped for rs 10822178 (-2712A/T) polymorphism and about 500 subjects were genotyped for all the other polymorphisms. Results: We found that the AA+AT genotype at the position -2712 conferred a 1.7-fold risk for LVH (OR 1.70, 95%CI 1.18-2.47, p=0.005), In the hypertensive patients, the AA and AT genotype carriers had a significant increase in their interventricular septal wall thickness (10.7±1.3mm for TT versus either 11.5±1.3mm for AA, P<0.01 or 11.2±1.4mm for AT, P<0.01 respectively in the hypertension patients with LVH; 9.2±1.6mm for TT versus either 9.9±1.6mm for AA, P<0.01 or 10.1±1.6mm for AT, P<0.01 respectively in the hypertension patients without LVH) and left ventricular mass index (57.4±11.7g/m^2.7 for TT ,61.8±15.8g/m^2.7 for AA, P<0.05 or 61.4±10.7g/m^2.7 for AT, P < 0.05 respectively in the hypertension patients with LVH; 46.8±13.8g/m^2.7 for TT, 48.8±16.8g/m^2.7 for AA, P<0.01 or 48.7±15.6g/m^2.7 for AT, P<0.01 respectively in the hypertension patients without LVH) after adjustment of age, sex, systolic and diastolic blood pressure and body mass index. No significant association was found between the other polymorphisms and echocardiographic variables in both hypertensive patients and in controls (P>0.05).Conclusions Our findings indicate that the -2712A/T polymorphism of the PKGâ… gene might be a genetic risk factor for the development of LVH in patients with hypertension.