[ACE gene polymorphism and cardiovascular diseases].
ABSTRACT The angiotensin converting enzyme (ACE) is an integral part of enzymatic cascades leading to generation of angiotensin II as well as degradation of bradykinin. For this reason, it represents an important part for the metabolism of 2 vasoactive peptides. Early in this decade, convincing experimental evidence demonstrated the induction of this enzyme in several pathophysiological conditions including myocardial infarction and left ventricular hypertrophy. In parallel, a deletion/insertion (D/I) polymorphism of the human ACE gene was discovered that was related to 14 to 50% of the interindividual variance of serum ACE activity. More recently, this polymorphism was implicated in the pathogenesis of a variety of cardiovascular disorders including myocardial infarction, left ventricular hypertrophy, hypertension as well as nephropathy.
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ABSTRACT: Genetic bases for novel prothrombotic, inflammatory risk factors may play a role in the early onset of coronary artery disease. Twenty-one patients below 35 years of age who underwent coronary bypass grafting between 2002 and 2004 constituted the study group and were compared with 50 healthy, age and sex-matched controls. Gene analysis for genetic polymorphisms of angiotensin-converting enzyme, prothrombin G20210A, tumour necrosis factor-alpha G308A, factor V Leiden and interleukin-6 genes was carried out. The control group was 98% homozygous for the factor V Leiden GG allele and 2% heterozygous for the GA allele. On the other hand, the study group was 76.2% homozygous for the GG allele, and 23.8% heterozygous for the GA allele (P<0.05). Homozygosity for factor V Leiden mutation (AA) was not encountered in either group. With regard to interleukin-6, 70.0% of the control group demonstrated homozygosity for the GG allele and 30.0% showed heterozygosity (GC). The study group was 52.4% homozygous for the GG allele and heterogenicity was similar in this group (28.6% GC). On the other hand, 19.0% of this group demonstrated CC homogenicity (P<0.05). No difference was observed with regard to gene polymorphisms. Gene polymorphisms with regard to prothrombotic factor V Leiden mutation and inflammatory marker interleukin-6 may play a role in the pathogenesis of early-onset coronary artery stenosis in patients below 35 years of age.Coronary Artery Disease 03/2006; 17(1):35-9. · 1.11 Impact Factor
Article: Pharmakogenomik[Show abstract] [Hide abstract]
ABSTRACT: In den letzten Jahren wurde der Verbesserung der Arzneimitteltherapie in der Pädiatrie zunehmend Aufmerksamkeit geschenkt. Nicht nur der Mangel an zugelassenen Arzneimitteln für Kinder, sondern auch der Ruf nach Optimierung des therapeutischen Effekts bei gleichzeitiger effektiver Vermeidung von schweren unerwünschten Arzneimittelwirkungen beschäftigen Ärzte/-innen, Pharmazeuten/-innen, pharmazeutische Industrie und Politik. Die Arzneimitteltherapie erfolgt derzeit im Wesentlichen empirisch. Ultimatives Ziel der Pharmakogenomik ist, basierend auf pharmakogenomischen Modellen eine rationale Verbesserung der Arzneimitteltherapie zu erreichen. Die Erstellung solcher Modelle erfordert die kritische Integration von Daten der funktionellen Genomik sowie molekularen Analysen und Daten der Pharmakokinetik und -dynamik. Anhand von zwei Beispielen, Behandlung der akuten lymphoblastischen Leukämie und Vermeidung von schweren unerwünschten Arzneimittelwirkungen, werden in diesem Beitrag generelle Strategien dargestellt, die zeigen, wie die Pharmakogenomik dazu beitragen kann, die Arzneimitteltherapie bei Kindern zu verbessern. Improvement of drug therapy in children has received special attention from pediatricians, pharmacists, the pharmaceutical industry, and policy makers during the last years. This attention was mainly driven by the lack of labeled medications for children and the well-recognized need to further enhance the efficacy and reduce the toxicity of medications. Drug therapy is essentially tailored empirically. The ultimate goal of pharmacogenomics is to individualize drug therapy based on pharmacogenomic models. Such models can be established by integrating data from functional genomics, molecular analyses, pharmacokinetics, and pharmacodynamics. Herein we provide two successful examples of the application of pharmacogenomic strategies in pediatrics, namely the treatment of acute lymphoblastic leukemia and the prevention of severe adverse drug reactions.Monatsschrift Kinderheilkunde 01/2008; 156(4):357-362. · 0.19 Impact Factor
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ABSTRACT: Survivors of myocardial infarction (MI) are known to have a high prevalence of arterial hypertension which, at the same time, imposes a major risk to such patients. Genetic variants of the arachidonic acid monooxygenase CYP4A11 may result in decreased synthesis of 20-hydroxyeicostatetraenoic acid (20-HETE), experimental hypertension and elevated blood pressure levels in humans. The present study aimed to investigate the impact of the functionally relevant T8590C polymorphism of this gene on blood pressure and the prevalence of hypertension in MI patients. Survivors of MI from the MONICA Augsburg MI registry (n = 560) were studied after a mean of 5.6 years after the acute event. Participants were examined by standardized anthropometric and echocardiographic measurements, as well as genotyping for CYP4A11 T8590C allele status. Genotype frequencies in MI patients (TT = 71.8%, CT = 26.2%, CC = 2.0%) did not differ from those in population-based controls (n = 1363; TT = 75.4%, CT = 22.5% and CC = 2.1%, P = 0.22). MI survivors with the CC genotype displayed higher systolic blood pressure levels (CC: 143.4 +/- 4.9 mmHg versus CT: 134.5 +/- 1.3 mmHg and TT: 131.1 +/- 0.8 mmHg; P = 0.02) and a non-significant trend towards higher diastolic blood pressure levels (CC: 88.4 +/- 3.0 mmHg versus CT: 84.9 +/- 0.8 mmHg and TT: 83.9 +/- 0.5 mmHg; P = 0.17) in multivariate models. Accordingly, the C allele was related to elevated odds ratios for hypertension in a recessive [4.14; 95% confidence interval (CI) = 1.07-15.96, P = 0.04] and in a dominant model (1.50; 95% CI = 1.03-2.20, P = 0.04), respectively. No blood pressure-independent association of the T8590C polymorphism with echocardiographic parameters of left ventricular function and/or geometry was found. The data obtained in the present study strengthen the evidence of an association of the CYP4A11 T8590C polymorphism with blood pressure levels and hypertension prevalence. Particularly, the risk of arterial hypertension is substantially higher in MI patients homozygous for the CC allele. By contrast, no evidence was obtained for an association between this genotype and MI.Journal of Hypertension 11/2006; 24(10):1965-70. · 4.22 Impact Factor