Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

A multilocus assay was used to genotype up to 27 variable sites in 15 genes in French and Italian, presumed to be healthy populations (n=1480, n=162, respectively). These genes are involved in lipid metabolism (APOE, APOB, APOC3, CETP, LPL, PON), homocysteine metabolism (CBS, MTHFR), blood viscosity (Fibrinogen, FV), platelet aggregation (GpIIIa), leukocyte adhesion (SELE), and renin-angiotensin system (AT1R, ACE, AGT). Allele frequencies for all the markers were compared between the two populations. Five allele frequencies differed between the two European countries: APOB 71Ile (p < 0.001), SELE 98T (p < 0.001), SELE 128Arg (p < or = 0.01), APOE E4 (p < or = 0.01) and MTHFR 677T (p < or = 0.01), suggesting the existence of a north-south gradient in European allele frequencies. The other allele frequencies : APOC3 -482T, -455C, 1100T, 3175G, 3206G; LPL -93G, 9Asn, 291Ser; CETP 405Val; PON 192Arg; ACE Del; AGT 235Thr; AT1R 1166C; CBS 278Thr, GpIIIa P1A2; Fibrinogen -455A, FV 506Gln and SELE 554Phe, were similar between the two populations. They were also similar to those observed in other European countries.
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PMID:Candidate gene polymorphisms in cardiovascular disease: a comparative study of frequencies between a French and an Italian population. 1134 49

The contribution of 17 polymorphisms within 13 candidate genes on lipid trait variability was investigated by a multiplex assay in 772 men and 780 women coming for a health checkup examination. The studied genes were APOE, APOB, APOC3, CETP, LPL, PON, MTHFR, FGB, GpIIIa, SELE, ACE, and AGT. We found that APOB-Thr71Ile, APOE-(112/158), APOC3-1100C/T, and SELE-98G/T polymorphisms had a significant effect on lipid traits (P < or = 0.001 to P < or = 0.01). Genetic effects accounted for 3.5-5.7% of variation in apolipoprotein B (apoB)-related traits among men, and for 5.7-9.0% among women. The contribution of APOE polymorphism on apoB-related traits variability was two to three times more important in women than in men. We found suggestive evidence for interactive effects between genetics and age, smoking status, and oral contraceptives. Increase of LDL-cholesterol and apoB concentrations with age was stronger among the epsilon4 carriers in women, and apolipoprotein A-I (apoA-I) concentration decreased with age in epsilon4 male carriers. The effect of epsilon2 allele on LDL-cholesterol was more important in the oral contraceptive users. In nonsmokers only, the APOC3-1100C allele in women was related to lower apoB-related traits concentrations, and in men to higher apoA-I and HDL-cholesterol concentrations. In conclusion, this work, in addition to the reinforcement of the already known associations between APOB, APOE, and APOC3 genes and lipids, leads to new perspectives in the complex relationships among genes and environmental factors. The newly observed relationships between E-selectine gene and lipid concentrations support the hypotheses of multiple metabolic pathways contributing to the complexity of lipids variability.
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PMID:Genetic influences on lipid metabolism trait variability within the Stanislas Cohort. 1171 57

Hypertension in pregnancy (HP), one of the most common causes of perinatal deaths, is a multifactorial disease with genetic and environmental factors involved in its etiology. We have carried out molecular epidemiologic research with the purpose of (1) identifying gene variants associated with HP in Japanese women, and (2) analyzing the genetic and environmental factors involved in the pathophysiology of the disease. Self-administered questionnaires were returned by the subjects between 1 and 6 months after delivery. The candidate genetic variants were identified by use of a PCR-RFLP method. T235 of AGT, C1166 of AT1 and Asp298 of NOS3 were respectively associated with HP, although no significant associations were found between the common genetic variants and HP in ACE, FV, MTHFR, B3AR, TNF-A, PAI-1, GSTP1, mEH, and LPL. In analyses using genetic, environmental and lifestyle factors, 5 factors before pregnancy and 4 factors during pregnancy were significantly associated with HP in univariate analysis. Further multivariate analysis revealed 3 factors before pregnancy, i.e. "prepregnancy BMI > or = 24 kg/m(2)", "family history of hypertension" and "TT genotype of AGT", and 2 factors during pregnancy, i.e. "mentally stressful condition" and "salty dishes preferred". Dividing the subjects into 2 subgroups according to whether they possessed "TT genotype of AGT" or not, we identified acquired risk factors before and during pregnancy for HP in each groups. The multivariate analysis identified "mentally stressful condition" as a potent significant risk factor during pregnancy in the former subgroup. However, there were no significant risk factors concerning and "mental stress" in the latter subgroup. Through further exploration of the risk factors associated with HP, we hope to provide useful suggestions about the development of new and effective preventive measures for a range of multifactorial diseases.
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PMID:Genetic and environmental factors associated with the development of hypertension in pregnancy. 1636 2

Although the risk for coronary heart disease (CHD) associated with single SNPs is modest it has been suggested that, in combination, several common risk-associated alleles could lead to a substantially better heart disease risk prediction. We have modelled this using 10 SNPs in ten candidate genes (APOB, NOS3, APOE, ACE, SERPINE1, MTHFR, ITGA2B, PON 1, LPL, and CETP) and their predicted summary risk estimates from meta-analysis. Based on published allele frequencies, approximately 29% of the general population would be expected to carry less than three risk alleles, approximately 55% would carry 3 or 4 risk alleles, 4% would have 6 and 1% 7 or more risk alleles. Compared to the mean of those with 3 or 4 risk associated genotypes, those with 6 and 7-or-more alleles have a significantly higher risk odds ratio (OR) of CHD (mean OR (95% Confidence Intervals), 1.70 (1.14 to 2.55); and 4.51 (2.89 to 7.04) respectively), while compared to those in the lowest decile of risk, those in the highest decile have a CHD odds ratio in the range of 3.05 (2.24 to 4.14). Taking into account age and the risk alleles carried, the mean 10 year probability for developing CHD for a 55 year old man was calculated to be 15% (8.6% to 24.8%), with nearly 1 in 5 having more than 20% risk. Whether this particular group of 10 SNPs will improve the accuracy of CHD predictions over the combination of classical risk factors in clinical use requires further experimental evidence.
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PMID:The use of meta-analysis risk estimates for candidate genes in combination to predict coronary heart disease risk. 1740 27

The impact of the ACE I/D polymorphism on coronary heart disease (CHD) risk is modest at most, however it may act as a modifier gene. ACE genotype was determined in 2711 healthy middle-aged men (mean age 56 years) followed for 15 years. No genotype-CHD risk association was found, but when analyzed by quartiles of systolic blood pressure (SBP), compared with II homozygotes, carriage of each additional D allele was protective at lower SBP, but in the highest quartile (SBP >150 mm Hg) conferred almost 1.5 times the risk for CHD (genotype interaction P=0.003). When SBP was analyzed as a continuous variable, again a highly significant association was seen, with the hazard ratio ([95% CI]) for a 1 SD increase in SBP being 0.90 [0.70 to 1.15] for IIs and 1.40 [1.21 to 1.61] for ID/DD (genotype SBP interaction P=0.002). The D allele was protective against CHD at lower SBP but would overtake the II risk at higher SBP. In hypertension, the proinflammatory or prohypertrophic properties of angiotensin II may explain this association. The LPL S447X polymorphism also impacts on CHD risk through interaction with hypertension, and there was an additive action of these 2 polymorphisms and SBP on CHD risk (hazard ratio for 1 SD increase in SBP for combined genotypes 1.78 [1.30 to 2.45]). Thus in the presence of hypertension, common variation in "modifier" genes confers significant CHD risk.
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PMID:Angiotensin-converting enzyme genotype interacts with systolic blood pressure to determine coronary heart disease risk in healthy middle-aged men. 1756 73

Single-gene disorders explain only a minority of stroke cases. Stroke represents a complex trait, which is usually assumed to be polygenic. On this topic, the role of a wide number of candidate genes has been investigated in stroke through association studies, with controversial results. Therefore, it is difficult for the clinician to establish the validity and the level of clinical applicability of the previously reported associations between genetic factors and stroke. This review is an update and an extensive analysis of the more recent association studies conducted in stroke. We evaluated a number of studies on several candidate genes (including F5, F2, FGA/FGB/FGG, F7, F13A1, vWF, F12, SERPINE1, ITGB3/PLA1/PLA2/ITGA2B, ITGA2, GP1BA, ACE, AGT, NOS3, APOE, LPL, PON1, PDE4D, ALOX5AP, MTHFR, MTR, and CBS), providing a final panel of genes and molecular variants. We categorized this panel in relation to the degree of association with stroke, supported by the results of meta-analyses and case-control studies. Our findings could represent a useful tool to address further molecular investigations and to realize more detailed meta-analyses.
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PMID:Genetic polymorphisms for the study of multifactorial stroke. 1842 1

With the aim to investigate association of polymorphisms of candidate genes with clinical peculiarities of hypertensive disease in patients having burdened familial anamnesis we examined 413 (229 men and 184 women, mean age 60.3 +/- 0.59 years) patients with essential arterial hypertension (AH). Determination of alleles and genotypes of polymorphic markers of ACE, AGT, AT2R1, CYP11B2, NOS3, ENDl, GNB3, PPARA, PPARG2, MTHFR, CAT, SOD2, PON1, PON2 sigma APOB, APOE, LPL genes was carried out with the use of polymerase chain reaction. Patient with AH having hereditary load were younger (58.9 +/- 0.75 and 61.3 +/- 0.89 years, respectively, p=0.017) and had significantly lower age of debut of the disease (44.4 +/- 0.84 and 47.5 +/- 1.03 years, respectively; p=0.013), higher values of systolic (204.8 +/- 7.66 and 187.0 +/- 2.04 mm Hg; p=0.032) and diastolic (111.2 +/- 1.05 and 107.3 +/- 1.17 mm Hg, respectively; p=0.025) arterial pressure (AP) compared with patients with AH without hereditary loaded anamnesis. Portion of patients with 3 degree of severity of AH was higher among patients with "familial" AH (53.6 and 44.1%, respectively, p=0.018). Early debut (in the age younger than 45 years in men and 55 years in women) was associated with carriage of genotype TT of polymorphic marker C825 of GNB3 gene (OR 2.65 95CI [1.27-5.54], p=0.005) and genotype AA of polymorphic marker A(A153)G of AT2R1 gene (OR 1.67 95% CI [1.03-2.77], p=0.024). Higher AP level corresponding to 3-rd degree AH in the group of patients with burdened familial anamnesis was associated with carriage of Asn allele of polymorphic marker Lysl98Asn of EDN1 gene (OR 2.24 95% CI [1.20-4.18], p=0.008), 4a allele of polymorphic marker 4a/4b of NOS3 gene (OR 2.23 C/[1.29-3.83], p=0.002), genotype ArgArg of polymorphic marker Glnl92Arg of PON1 gene (OR 6.14 C7[1.46-25.67], p=0.01), T allele of polymorphic marker of C825T gene GNB3 (OR 1.75 C/[1.11-2.76], p=0.01) and genotype AA of polymorphic marker A(A153)G of AT2R1 gene (OR 2.61 C/11.29-5.34], p=0.005). In patients without burdened familial anamnesis 3-rd degree AH was associated with higher frequency of allele Ala of polymorphic marker Pro12A1a of PPARG2 gene.
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PMID:[Association of genetic factors with clinical peculiarities of hypertensive disease in patients with burdened familial anamnesis]. 1925 15

Carriage frequencies of alleles and genotypes of 10 functionally important single nucleotide polymorphisms that are located in genes FGA, FGB, APOE, LPL, ACE and CMA1 were analyzed in the ischemic stroke (IS) patients of Russian ethnic descent and in the control group of the same ethnic descent and of similar gender and age. Comparison between patients and control group revealed no significant differences in frequencies of individual alleles and genotypes for all the polymorphic loci studied. However, complex analysis of genetic predisposition using APSampler algorithm revealed carriage of allele (-491A) APOE as a predisposing factor for IS (p = 0.044, OR 3.8, 95% CI 1.0-15.1). Accordingly, carriage of genotype (-491T/T) APOE was associated with resistance to IS (p = 0.044, OR 0.26, 95% CI 0.07-1.0). The allele -249C FGB carriage addition to this genotype enhances its protective properties, p-value of the combination is 2-fold lower than that of the genotype (-491T/T) APOE (OR 0.17, 95% CI 0.04-0.8). Two more protective combinations were identified: biallelic (-427C) APOE + (1595G) LPL and triallelic (-491C) APOE + (1595G) LPL + (-1903G) CMAI (in both cases p = 0.0052, OR 0.18, 95% CI 0.05-0.66). Overall, involvement in formation of the risk of IS development in Russians was evidenced for alleles of four genes: APOE, FGB, LPL and CMA1, where APOE gene involvement was evidenced for alleles of two polymorphic loci, -491T and -427C. Linkage analysis suggested that involvement of these loci in insusceptibility to IS is mutually independent.
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PMID:[Complex analysis of genetic predisposition to ischemic stroke in Russians]. 1989 40

BACKGROUND Pre-eclampsia has a clear familial component, suggesting that the condition may be partly attributable to genetic susceptibility. The search for susceptibility genes has led to a drastic increase in the number of published studies associating genetic factors with pre-eclampsia. However, attempts to replicate these findings have yielded inconsistent results. This meta-analysis assessed the pooled effect of each genetic variant that is reproducibly associated with pre-eclampsia. METHODS Studies that assessed the association between genes and pre-eclampsia were searched in PubMed, Embase and Web of Science. We selected all genetic variants that were significantly associated with pre-eclampsia in an initial study and were subsequently independently reproduced in at least one additional study. All studies that assessed these reproduced variants were then included. The association between genetic variants and pre-eclampsia was calculated at the allele level, and the main measure of effect was a pooled odds ratio in a random-effects model. RESULTS The literature search yielded 2965 articles, of which 542 investigated genetic associations in pre-eclampsia. We identified 22 replicated genetic variants, of which 7 remained significantly associated with pre-eclampsia following meta-analysis. These variants were in or near the following genes: ACE, CTLA4, F2, FV, LPL and SERPINE1. CONCLUSIONS This meta-analysis identified seven genetic variants associated with pre-eclampsia. Importantly, many of these variants are also risk factors for developing cardiovascular disease, revealing that pre-eclampsia and cardiovascular disease have shared genetic risk factors. The contribution of the identified genetic variants in the pathogenesis of pre-eclampsia should be the focus of future studies.
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PMID:Genetic variants in pre-eclampsia: a meta-analysis. 2393 Feb 69

The presence of a silencing sequence (the I-allele) in the gene for the upstream regulator of blood flow, angiotensin I-converting enzyme (ACE), is associated with superior endurance performance and its trainability. We tested in a retrospective study with 36 Caucasian men of Swiss descent whether carriers of the ACE I-allele demonstrate a modified adaptive response of energy supply lines in knee extensor muscle, and aerobic fitness, to endurance training based on 6 weeks of supervised bicycle exercise or 6 months of self-regulated running (p value <Bonferroni-corrected 5%). Body weight related maximal oxygen uptake and capillary density in vastus lateralis muscle before training were 20 and 23% lower, respectively, in carriers of the I-allele. Bicycle (n = 16) but not running type endurance training (n = 19) increased the volume content of subsarcolemmal mitochondria (2.5-fold) and intramyocellular lipid (2.1-fold). This was specifically amplified in I-allele carriers after 6 weeks of bicycle exercise. The enhanced adjustment in myocellular organelles of aerobic metabolism with bicycle training corresponded to ACE I-allele dependent upregulation of 23 muscle transcripts during recovery from the bicycle stimulus and with training. The majority of affected transcripts were associated with glucose (i.e. ALDOC, Glut2, LDHC) and lipid metabolism (i.e. ACADL, CPTI, CPTII, LIPE, LPL, FATP, CD36/FAT); all demonstrating an enhanced magnitude of change in carriers of the ACE I-allele. Our observations suggest that local improvements in mitochondrial metabolism, through a novel expression pathway, contribute to the varying trainability in endurance performance between subjects with genetically modified expression of the regulator of vascular tone, ACE.
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PMID:The angiotensin converting enzyme insertion/deletion polymorphism alters the response of muscle energy supply lines to exercise. 2339 51


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