Lack of Association Between a Polymorphism of the Aldosterone Synthase Gene and Left Ventricular Structure

Schunkert, Heribert; Hengstenberg, Christian; Holmer, Stephan; Broeckel, Ulrich; Luchner, Andreas; Muscholl, M.; Kürzinger, Susanne; Döring, Angela; Hense, Hans‐Werner; Riegger, Günter A.J.

doi:10.1161/01.cir.99.17.2255

Cited by 102 publications

(94 citation statements)

References 23 publications

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“…In keeping with the results of earlier studies, the associations of the CYP11B2 C-344T polymorphism with BP remain inconclusive. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] In addition, our results were not consistent with previous reports indicating that BP elevation was sensitive in elderly subjects with the TT genotype. 20,21 Furthermore, we suggested that the association of the CC genotype with CRP was consistent with previous reports describing the association of the genotype with cardiac structures and atherosclerosis as discussed above, 17,34 whereas some apparent contradictory associations between the genotype and atherosclerosis, including cardiac structure and coronary artery diseases, have been shown in previous studies.…”

Section: Discussioncontrasting

confidence: 99%

“…3 An overview of published studies suggests a higher frequency of hypertension or increase in blood pressure (BP) in subjects with the T allele or TT genotype as compared with that in subjects with the C allele or CC genotype, [4][5][6][7][8][9][10] although several studies have reported the opposite association 11,12 or the absence of any association. [13][14][15][16][17][18][19] Thus, the associations remain controversial. Recently, two interesting studies have suggested a key indicator that may resolve the association.…”

Section: Introductionmentioning

confidence: 99%

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Aldosterone synthase (CYP11B2) C-344T polymorphism affects the association of age-related changes of the serum C-reactive protein

et al. 2010

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Aldosterone participates in vascular and myocardial inflammation either directly or indirectly through blood pressure (BP). Aldosterone synthase (CYP11B2) C-344T polymorphism may influence the severity of systemic inflammation. A total of 398 Japanese Americans (152 men and 246 women, age 19-92 years) from the Hawaii-Los Angeles-Hiroshima study were enrolled. BP and serum levels of C-reactive protein (CRP) were measured, and the CYP11B2 C-344T polymorphism, rs1799998, was determined. No influence of the polymorphism on baseline characteristics such as systolic, diastolic and mean BP, pulse pressure or serum CRP levels was observed. In all genotypes, systolic BP showed a significantly positive correlation with age (TT (n¼178): r¼0.283, Po0.001; TC (n¼164): r¼0.213, P¼0.006; and CC (n¼56): r¼0.289, P¼0.031). However, the regression coefficients of systolic BP with age were not different across genotypes. According to the results of univariate and multivariate analyses with adjustment for BP, the serum CRP level increased with age only in subjects with the CC genotype (P¼0.027 and P¼0.004, respectively), and elevation of serum CRP was mainly observed in the elderly population (aged X60 years). Moreover, the regression coefficient of CRP levels with age was significantly steeper in subjects with the CC genotype than in those with the TC or TT genotype (P¼0.028). The CC genotype of the CYP11B2 C-344T polymorphism was associated with an age-dependent increase in the serum CRP level independent of BP, and may contribute to a cardiovascular phenotype by promoting vascular inflammation.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Aldosterone synthase (CYP11B2) C-344T polymorphism affects the association of age-related changes of the serum C-reactive protein

et al. 2010

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“…A subsequent study on a larger but older population failed to confirm the association between C(À344)T polymorphism and BP, cardiac measurements, and aldosterone levels. 2 Further contradictory results came from another paper that described both a linkage study on hypertensive sibships and a casecontrol study. 3 These studies, based on older populations than Kupari's, 1 failed in finding a linkage of hypertension with CYP11B2 alleles, but found a positive association of the T(À344) allele with hypertension.…”

Section: Introductionmentioning

confidence: 99%

Aldosterone synthase alleles and cardiovascular phenotype in young adults

et al. 2003

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The C(À344)T promoter polymorphism of the human aldosterone synthase (CYP11B2) gene has been associated with hypertension and cardiac hypertrophy, but there were contrasting data. We analysed the genotype/ phenotype associations between this polymorphism and cardiovascular variables in a young adult population, where interactions among genes, gene-environment, and acquired ageing-related organ damage are reduced. Anthropometric measurements, blood pressure, heart rate, left ventricular variables (by echocardiography), and carotid artery wall intimal-media thickness (by high-resolution sonography and digitalized morphometry) were taken in 420 white Caucasian students (mean age 23.5 years, s.d. 2.5 years). CYP11B2 alleles were detected by genomic polymerase chain reaction followed by digestion. Taking into account the three possible models of inheritance, we found no differences in the considered variables, except for an independent effect of the C(À344) allele on SBP in males (TT 125.6 (1.6), TC 128.4 (1.2) and CC 130.5 (2.2), mmHg, media (ES), P ¼ 0.03), and on interventricular septum thickness in diastole in females (CC 6.98 (0.12) vs TT 6.87 (0.09) and TC 6.87 (0.07), mmHg, Po0.01), in the codominant model. In conclusion, the CYP11B2 C(À344)T polymorphism appears to have a slight role in the cardiovascular phenotype of young healthy adults, even if these genotype/phenotype relationships might change with ageing.

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“…73 Although one small study confirmed this association, 74 other larger studies failed to detect a significant effect of this polymorphism on left ventricular structure. 75,76 Mayosi et al 77 investigated the contribution of several markers in the CYP11B2 gene, including the C-344T polymorphism, as individual variants and haplotypes. Polymorphisms and haplotypes at the CYP11B2 locus were associated with a small but significant effect on variation in septal wall thickness and left ventricular cavity size (variants G5937C and A4450C respectively).…”

Section: Aldosterone Synthase C-344t Polymorphismmentioning

confidence: 99%

Genetic polymorphisms and heart failure

Bleumink

Schut

Sturkenboom

et al. 2004

Genetics in Medicine

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Heart failure is a complex clinical syndrome. There is evidence for a genetic contribution to the pathophysiology of heart failure. Considering the fundamental role of neurohormonal factors in the pathophysiology and progression of cardiac dysfunction and hypertrophy, variants of genes involved in this system are logical candidate genes in heart failure. In this report, genetic polymorphisms of the major neurohormonal systems in heart failure will be discussed. Studies on polymorphisms of the renin-angiotensin-aldosterone system (RAAS), adrenergic receptor polymorphisms, endothelin (receptor) polymorphisms, and a group of miscellaneous polymorphisms that may be involved in the development or phenotypic expression of heart failure will be reviewed. Research on left ventricular hypertrophy is also included. The majority of genetic association studies focused on the ACE I/D polymorphism.Initial genetic associations have often been difficult to replicate, mainly due to problems in study design and lack of power. Promising results have been obtained with genetic polymorphisms of the RAAS and sympathetic system.Considering the evidence so far, a modifying role for these polymorphisms seems more likely than a role of these variants as susceptibility genes. Besides the need for larger studies to examine the effects of single nucleotide polymorphisms and haplotypes, future studies also need to focus on the complexity of these systems and study Heart failure is a complex clinical syndrome with high morbidity and mortality. 1,2 Impairment of cardiac function activates compensatory neurohormonal mechanisms, which at a later stage may accelerate progression of heart failure. 3 Coronary heart disease and hypertension are major underlying causes of heart failure. Other frequent underlying conditions include valvular heart disease and idiopathic dilated cardiomyopathy. It is difficult to predict who will develop heart failure in response to myocardial injury. Racial differences in occurrence and outcome of heart failure 4,5 and heritability estimates of variability in left ventricular mass of 28% to 65% 6,7 suggest a genetic contribution to the pathophysiology of left ventricular remodeling and heart failure.Many studies have been published on the role of single gene mutations in (familial) cardiomyopathies. 8,9 These Mendelian traits are by nature rare, and although important at an individual level and for the understanding of disease mechanisms, are of limited significance in terms of prediction of heart failure occurrence in the population. 10 Moreover, in patients with identical gene mutations clinical manifestations of cardiomyopathy may differ. This suggests that probably also environmental and/or other genetic factors play a role.In this report, genetic polymorphisms of major neurohormonal systems involved in the pathophysiology of heart failure will be discussed, including the renin-angiotensin-aldosterone system (RAAS), adrenergic receptor polymorphisms, endothelin (receptor) polymorphisms, and a group of miscellaneous...

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Lack of Association Between a Polymorphism of the Aldosterone Synthase Gene and Left Ventricular Structure

Cited by 102 publications

References 23 publications

Aldosterone synthase (CYP11B2) C-344T polymorphism affects the association of age-related changes of the serum C-reactive protein

Aldosterone synthase (CYP11B2) C-344T polymorphism affects the association of age-related changes of the serum C-reactive protein

Aldosterone synthase alleles and cardiovascular phenotype in young adults

Genetic polymorphisms and heart failure

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