Biomedical subjects

Anna F C Schut

Publications and source records attributed to Anna F C Schut.

4 recordsLinked to original sources

PubMed2005

Mortality in patients with hypertension on angiotensin-I converting enzyme (ACE)-inhibitor treatment is influenced by the ACE insertion/deletion polymorphism.

BACKGROUND: The response to angiotensin-I converting enzyme (ACE)-inhibitor therapy is highly variable. Residual ACE activity during treatment, potentially modified by the ACE insertion/deletion (I/D) polymorphism, may explain part of this variability. We studied the possible interaction between ACE-inhibitor therapy in patients with hypertension and the ACE I/D polymorphism in incident heart failure and death. METHODS: We studied 3365 hypertensive participants of the population-based Rotterdam Study, without heart failure at baseline for whom ACE-genotyping was successful. Incident heart failure was defined according to established criteria. In addition, total and cardiovascular mortality were studied as endpoints. A Cox regression model with use of ACE-inhibitors defined as time-dependent covariates was used for data-analysis. Interaction was tested in this model assuming an allele-effect relationship. RESULTS: Although we could not demonstrate a beneficial effect of ACE-inhibitors, there was significant interaction between the ACE I/D polymorphism (II-ID-DD) and ACE-inhibitor use in the prediction of total and cardiovascular mortality. Mortality risk associated with treatment increased with the number of D alleles present; e.g. for total mortality in the II genotype group: RR=0.95 (95% CI 0.63-1.45), in the ID genotype group: RR=1.08 (95% CI 0.84-1.38) and in the DD genotype group: RR=1.61 (95% CI 1.18-2.18). No statistically significant interaction was found for incident heart failure. CONCLUSION: The results of our study suggest a relative resistance to ACE-inhibitor therapy in subjects with hypertension and the DD genotype compared to the II genotype, with the ID genotype in an intermediate position.

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PubMed2004

Angiotensin converting enzyme insertion/deletion polymorphism and the risk of heart failure in hypertensive subjects.

AIMS: Cardiac angiotensin-I converting enzyme (ACE) activity is influenced by the ACE I/D polymorphism. Evidence suggests that the DD-genotype may be a risk factor for cardiac hypertrophy and heart failure, especially in hypertensive subjects. We assessed the relation between the ACE I/D polymorphism and the risk of incident heart failure in normotensive and hypertensive subjects. METHODS AND RESULTS: We investigated 4264 normotensive and 2174 hypertensive participants of the Rotterdam Study, a population based prospective cohort study. All subjects were available for follow-up from 1990 until 2000. Incidence rates (IR) of heart failure in normotensive subjects were the same over all genotype strata (10 per 1000 person-years). In hypertensive subjects, the IR increased with the number of D-alleles present (II: IR=13, ID: IR=18 and DD: IR=20 per 1000 person-years). Hypertensive subjects carrying the II-genotype did not have an increased risk of heart failure compared to normotensive II subjects. However, hypertensive subjects carrying one or two copies of the D-allele did have a significantly increased risk of heart failure (ID: RR: 1.4 (1.1-1.9) and DD: RR: 1.5 (1.2-2.1)). CONCLUSION: Our findings suggest that the ACE I/D polymorphism may play a modifying role in the development of heart failure in hypertensive subjects.

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PubMed2004

Smoking-dependent effects of the angiotensin-converting enzyme gene insertion/deletion polymorphism on blood pressure.

BACKGROUND: Studies on the role of the angiotensin-converting enzyme (ACE) gene in the development of hypertension have yielded conflicting results. Recent studies suggested that this gene might have smoking-dependent effects on the development of cardiovascular disease. OBJECTIVE: To study the relationship between the ACE insertion/deletion (I/D) polymorphism, blood pressure and risk of hypertension in current, former and non-smokers in a population-based cohort. METHODS: We included 2412 non-smokers, 2794 former smokers and 1508 current smokers, all participants in the Rotterdam Study. In each group, we assessed the relationship between the ACE I/D polymorphism, systolic (SBP) and diastolic (DBP) blood pressures and risk of hypertension. Mean blood pressures and prevalence of hypertension were compared between carriers and non-carriers of the D allele. All analyses were adjusted for age, sex, body mass index, diabetes mellitus, high-density lipoprotein cholesterol, total cholesterol and use of antihypertensive medication. RESULTS: In non-smokers and former smokers, blood pressure and the risk of hypertension did not differ significantly between genotypes. In smokers, we found a significant increase in SBP in DD carriers (139.6 +/- 22.8 mmHg) compared with II carriers (136.0 +/- 22.7 mmHg) (P = 0.04). No effect of ACE genotype was observed for DBP. The risk of hypertension was significantly increased in smokers who carried one [odds ratio (OR) 1.4, 95% confidence interval (CI) 1.0 to 1.9; P = 0.05] or two (OR 1.5, 95% CI 1.1 to 2.2; P = 0.02) copies of the D allele. CONCLUSIONS: The D allele of the ACE polymorphism is associated with a significantly increased SBP and risk of hypertension in smokers. Our study underlines the importance of gene-environment interactions in the study of candidate genes for hypertension.

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PubMedDate not supplied

Genetic polymorphisms and heart failure.

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 gene-gene interactions and gene-environment interactions.

Heart Failure↗