Dataset Information

Variation in eicosanoid genes, non-fatal myocardial infarction and ischemic stroke.

ABSTRACT: OBJECTIVES:Eicosanoids are lipid mediators that may play a role in atherosclerosis. We investigated the association of common genetic variation in prostaglandin H synthase 1 (PTGS1), prostaglandin H synthase 2 (PTGS2), thromboxane A2 synthase (TBXAS1), prostacyclin synthase (PTGIS), prostaglandin E synthase (PTGES), 5-lipoxygenase activating protein (ALOX5AP), 12-lipoxygenase (ALOX12) and 15-lipoxygenase (ALOX15) with the risks of myocardial infarction (MI) and ischemic stroke. A secondary aim was to replicate the interaction of PTGS2 rs20417 (-765G to C) with aspirin use on coronary heart disease risk observed in the Atherosclerosis Risk in Communities Study (ARIC). METHODS:We conducted a case-control study in a large Health Maintenance Organization. Cases were men and women, aged 30-79 years with incident non-fatal myocardial infarction (n=1063) or ischemic stroke (n=469) between January 1995 and December 2004. Controls (n=3462) were randomly selected and frequency matched to cases on age, sex, hypertension and calendar year. RESULTS:Common variation in TBXAS1 and PTGIS was associated with MI risk (p-value for global Chi-square test, 0.01 and 0.03, respectively). Common variation in ALOX5AP, ALOX12, ALOX15, PTGS1, PTGS2 and PTGES was not associated with risks of MI and ischemic stroke. We replicated the observation of the Atherosclerosis Risk in Communities Study and observed an interaction of rs20417 with aspirin use on myocardial infarction risk (p for interaction=0.03). CONCLUSIONS:Study results suggest that variation in TBXAS1 and PTGIS may influence MI risk, and carriers of rs20417C allele might derive greater benefits from aspirin use in primary prevention.

SUBMITTER: Lemaitre RN

PROVIDER: S-EPMC2753183 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

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Variation in eicosanoid genes, non-fatal myocardial infarction and ischemic stroke.

Lemaitre Rozenn N RN Rice Kenneth K Marciante Kristin K Bis Joshua C JC Lumley Thomas S TS Wiggins Kerri L KL Smith Nicholas L NL Heckbert Susan R SR Psaty Bruce M BM

Atherosclerosis 20081101 2

<h4>Objectives</h4>Eicosanoids are lipid mediators that may play a role in atherosclerosis. We investigated the association of common genetic variation in prostaglandin H synthase 1 (PTGS1), prostaglandin H synthase 2 (PTGS2), thromboxane A2 synthase (TBXAS1), prostacyclin synthase (PTGIS), prostaglandin E synthase (PTGES), 5-lipoxygenase activating protein (ALOX5AP), 12-lipoxygenase (ALOX12) and 15-lipoxygenase (ALOX15) with the risks of myocardial infarction (MI) and ischemic stroke. A seconda ...[more]

PMID: 19046748

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Project description:Although Cholesteryl Ester Transfer Protein (CETP) mediates the transfer of cholesteryl esters and triglycerides between lipoprotein particles and thus plays a crucial role in reverse cholesterol transport, the association of variations in the CETP gene with acute myocardial infarction (MI) remains unclear. In this study we examined whether common genetic variation in the CETP gene is related to early-onset non-fatal MI risk in a population-based case-control study from western Washington State. Genotyping for the CETP -2708 G/A, -971 A/G, -629 A/C, Intron-I TaqI G/A and exon-14 A/G (I405V) SNPs was performed in 578 cases with first acute non-fatal MI and in 666 demographically similar controls, free of clinical cardiovascular disease, identified randomly from the community. In-person interviews and non-fasting blood specimens provided data on coronary heart disease risk factors. In men, there was little evidence for an association between single SNPs and MI risk, but in women the age- and race-adjusted OR was found to be significant in 4 out of the 5 CETP single variants. Haplotype analysis revealed two haplotypes associated with MI risk among men. As compared to men homozygous for the most common haplotype D (-2708 G, -971 G, -629 C, TaqI G and exon-14 A), the fully-adjusted multiplicative model identified haplotype G (-2708 G, -971 A, -629 A, TaqI G and exon-14 G) was associated with a 4.0-6.0-fold increased risk of MI for each additional copy; [95%CI 2.4-14.8] and haplotype B (-2708 G, -971 G, -629 A, TaqI A and exon-14 A) showed a significant decreased risk for early onset MI [OR = 0.18; 95%CI 0.04 - 0.75]. An evolutionary-based haplotype analysis indicated that the two haplotypes associated with the MI risk are most evolutionarily divergent from the other haplotypes. Variation at the CETP gene locus is associated with the risk of early-onset non-fatal MI. This association was found to be independent of HDL-C levels. These data and the sex-specific findings require confirmation in other populations.

Project description:RationalePrevious studies have suggested that acute exacerbations of chronic obstructive pulmonary disease (COPD) may be associated with increased risk of myocardial infarction and ischemic stroke.ObjectivesWe aimed to quantify the increased risks of myocardial infarction and ischemic stroke risk associated with both moderate and severe acute exacerbation, and to investigate factors that may modify these risks.MethodsWe performed a self-controlled case series to investigate the rates of myocardial infarction and ischemic stroke after acute exacerbation compared with stable time, within individuals. The participants were 5,696 adults with COPD with a first myocardial infarction (n = 2,850) or ischemic stroke (n = 3,010) and at least one acute exacerbation from the UK Clinical Practice Research Datalink with linked Hospital Episodes Statistics data.ResultsThe risks of both myocardial infarction and ischemic stroke were increased in the 91 days after an acute exacerbation. The risks were greater after a severe exacerbation (incidence rate ratio [IRR], 2.58; 95% confidence interval [CI], 2.26-2.95 for myocardial infarction; and IRR, 1.97; 95% CI, 1.66-2.33 for ischemic stroke) than after a moderate exacerbation (IRR, 1.58; 95% CI, 1.46-1.71 for myocardial infarction; and IRR, 1.45; 95% CI, 1.33-1.57 for ischemic stroke). The relative risks of myocardial infarction and ischemic stroke associated with acute exacerbation were lower among those with more frequent exacerbations (IRR, 1.42; 95% CI, 1.24-1.62 vs. IRR, 1.69; 95% CI, 1.50-1.91 for myocardial infarction; and IRR, 1.30; 95% CI, 1.15-1.48 vs. IRR, 1.68; 95% CI, 1.50-1.89 for ischemic stroke). Higher GOLD stage was associated with a lower rate of myocardial infarction (IRR, 1.98; 95% CI, 1.61-2.05 vs. IRR, 1.69; 95% CI, 1.45-1.98) but not for ischemic stroke. Aspirin use at baseline was associated with a lower risk of ischemic stroke (IRR, 1.28; 95% CI, 1.10-1.50 vs. IRR, 1.63; 95% CI, 1.47-1.80) but not with myocardial infarction.ConclusionsAcute exacerbations of COPD are associated with an increased risk of myocardial infarction and ischemic stroke within 28 days of their onset. Several patient characteristics were identified that are associated with these events.

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Variation in eicosanoid genes, non-fatal myocardial infarction and ischemic stroke.

Publications

Variation in eicosanoid genes, non-fatal myocardial infarction and ischemic stroke.

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