Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We sought evidence of publication bias to explain conflicting findings in studies of angiotensin-converting enzyme deletion polymorphism (ACE D) and glycoprotein IIIa PlA2 (PLA2) polymorphism and the risk of myocardial infarction. Factor 5 Leiden (F5L), a well-established thrombotic risk factor, served as an internal comparison. We conducted systematic reviews of published studies involving ACE D, PLA2, F5L and relevant outcomes, searching medline (January 1990 through February, 2001), bibliographies, and meta-analyses. Random effects pooled odds ratios (95% confidence interval) for cardiovascular outcomes were as follows: PLA2 (n = 13,167 subjects): 1.13 (1.02, 1.26); ACE D (n = 42,140 subjects): 1.22 (1.11, 1.35); and F5L (n = 27,277 subjects): 4.43 (3.65, 5.38). However, funnel plots of ACE D and PLA2, but not F5L, showed an inverse relationship between sample size and odds ratios for ACE D (p = 0.02) and PLA2 (p = 0.04) but not F5L (p = 0.65) by Egger's test for potential publication bias. Despite research-based genotyping of over 50,000 subjects, the overall risk for myocardial infarction as a result of PLA2 and ACE D remains doubtful. Our study provides a clear example of how publication of underpowered studies can spuriously implicate polymorphisms as genetic risk factors.
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PMID:Overestimation of genetic risks owing to small sample sizes in cardiovascular studies. 1279 Oct 34

There are a total of 17 families of drugs that are used for treating the heterogeneous group of cardiovascular diseases. We propose a comprehensive pharmacogenomic approach in the field of cardiovascular therapy that considers the five following sources of variability: the genetics of pharmacokinetics, the genetics of pharmacodynamics (drug targets), genetics linked to a defined pathology and its corresponding drug therapies, the genetics of physiologic regulation, and environmental-genetic interactions. Examples of the genetics of pharmacokinetics are presented for phase I (cytochromes P450) and phase II (conjugating enzymes) drug-metabolizing enzymes and for phase III drug transporters. The example used to explain the genetics of pharmacodynamics is glycoprotein IIIa and the response to antiplatelet effects of aspirin. Genetics linked to a defined pathology and its corresponding drug therapies is exemplified by ADRB1, ACE, CETP and APOE and drug response in metabolic syndrome. The examples of cytochrome P450s, APOE and ADRB2 in relation to ethnicity, age and gender are presented to describe genetics of physiologic regulation. Finally, environmental-genetic interactions are exemplified by CYP7A1 and the effects of diet on plasma lipid levels, and by APOE and the effects of smoking in cardiovascular disease. We illustrate this five-tiered approach using examples of cardiovascular drugs in relation to genetic polymorphism.
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PMID:Pharmacogenomics and drug response in cardiovascular disorders. 1546 3

Genetic polymorphisms may affect platelets' responses to the antiplatelet therapy. Our aim was to determine the role of genetic polymorphisms on aspirin resistance in patients with coronary heart disease (CHD). A total of 126 consecutive patients (35-85 years old, 32% women) with chronic stable CHD was enrolled in the study. Platelet function assays were realized by the platelet function analyzer (PFA)-100 with collagen and epinephrine (Col/Epi) and collagen and adenosine diphosphate (Col/ADP) cartridges. Aspirin resistance was defined as having a closure time of less than 186 s with Col/Epi cartridges despite regular aspirin therapy. Factor V, prothrombin, factor XIII, beta-fibrinogen, plasminogen activator inhibitor I (PAI-1), glycoprotein IIIa, methylene tetrahydrofolate reductase, ACE and ApoB gene polymorphisms were determined by three consecutive steps: isolation and amplification of DNA and reverse hybridization. We determined that 30 patients (23.8%) had aspirin resistance by the PFA-100. Mean closure time measured with the Col/ADP cartridges was 74 +/- 12 s (51-104 s). Ten of the 30 patients with aspirin resistance were women (33.3%). Genetic polymorphisms were determined in 30 aspirin-resistant and 17 aspirin-sensitive patients. No statistically significant relationship was determined between aspirin resistance and the genetic panel. In our study we did not determine a significant relationship between the aspirin resistance and factor V, prothrombin, factor XIII, beta-fibrinogen, PAI-1, glycoprotein IIIa, methylene tetrahydrofolate reductase, ACE and ApoB gene polymorphisms.
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PMID:Impact of genetic polymorphisms on platelet function and aspirin resistance. 1992 80

Interrelationships between genetic and biochemical factors underlying ischemic stroke and ischemic heart disease are poorly understood. We: 1) undertook the most comprehensive meta-analysis of genetic polymorphisms in ischemic stroke to date; 2) compared genetic determinants of ischemic stroke with those of ischemic heart disease, and 3) compared effect sizes of gene-stroke associations with those predicted from independent biochemical data using a mendelian randomization strategy. Electronic databases were searched up to January 2009. We identified: 1) 187 ischemic stroke studies (37,481 cases; 95,322 controls) interrogating 43 polymorphisms in 29 genes; 2) 13 meta-analyses testing equivalent polymorphisms in ischemic heart disease; and 3) for the top five gene-stroke associations, 146 studies (65,703 subjects) describing equivalent gene-biochemical relationships, and 28 studies (46,928 subjects) describing biochemical-stroke relationships. Meta-analyses demonstrated positive associations with ischemic stroke for factor V Leiden Gln506, ACE I/D, MTHFR C677T, prothrombin G20210A, PAI-1 5G allele and glycoprotein IIIa Leu33Pro polymorphisms (ORs: 1.11 - 1.60). Most genetic associations show congruent levels of risk comparing ischemic stroke with ischemic heart disease, but three genes--glycoprotein IIIa, PAI-1 and angiotensinogen--show significant dissociations. The magnitudes of stroke risk observed for factor V Leiden, ACE, MTHFR and prothrombin, but not PAI-1, polymorphisms, are consistent with risks associated with equivalent changes in activated protein C resistance, ACE activity, homocysteine, prothrombin, and PAI-1 levels, respectively. Our results demonstrate causal relationships for four of the most robust genes associated with stroke while also showing that PAI-1 4G/5G polymorphism influences cardiovascular risk via a mechanism not simply related to plasma levels of PAI-1 (or tPA) alone.
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PMID:Causal relationship of susceptibility genes to ischemic stroke: comparison to ischemic heart disease and biochemical determinants. 2016 34

Venous thrombosis is a significant cause of morbidity and mortality in patients with malignancies. We aimed to investigate the association between prothrombotic gene polymorphisms detected in lung cancer cases and deep venous thrombosis (DVT). Totally 66 patients with an established diagnosis of lung cancer, of which 33 developed DVT, were enrolled. Multiplex PCR technique and reverse hybridization strip assay were performed on DNA extracted from peripheral blood, in order to analyze prothrombin G20210A, factor V G1691A, methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, angiotensin converting enzyme (ACE), plasminogen activator inhibitor-1 (PAI-1), and glycoprotein IIIa (Gp IIIa) gene mutations. Among prothrombotic gene polymorphisms investigated in this study, the commonest ones were PAI-1 4G/5G (56% heterozygous, 39% homozygous) and ACE gene mutations (58% heterozygous, 17% homozygous). The presence of homozygous MTHFR A1298C mutation was significantly associated with DVT (P=0.020). Comparing the lung cancer patients with and without DVT, only MTHFR A1298C gene polymorphism differed significantly (P=0.040). We determined a higher rate of prothrombotic gene mutations in lung cancer patients who developed DVT. However, statistical significance was achieved only for MTHFR A1298C gene mutation. Therefore, nongenetic factors for disturbance of hemostatic metabolism should also be considered in lung cancer patients.
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PMID:Association of deep venous thrombosis with prothrombotic gene polymorphism identified in lung cancer cases. 2108 81