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Association of PLA2G4A with myocardial infarction is modulated by dietary PUFAs.

ABSTRACT: Leukotrienes are proinflammatory molecules derived from dietary PUFAs and have been associated with cardiovascular disease (CVD). We previously reported that an A?G variant (rs12746200) of the cytosolic phospholipase A2 group IVA gene (PLA2G4A), which encodes the enzyme that liberates PUFAs from cellular membranes for leukotriene synthesis, decreases the risk of CVD.We sought to replicate these initial observations with a more clinically relevant phenotype, such as myocardial infarction (MI), and to determine whether dietary PUFAs mediate this association.In a Costa Rican case-control data set (n = 3971), rs12746200 was genotyped and was tested for an association with MI. Functional experiments were carried out to determine whether rs12746200 led to differences in mRNA expression.Risk of MI was significantly lower in AG/GG subjects than in AA homozygotes (OR: 0.86; 95% CI: 0.75, 0.99; P = 0.040). The reduced risk of MI was observed primarily in AG/GG subjects who were above the median for intake of dietary omega-6 (n-6) PUFAs (OR: 0.71; 95% CI: 0.59, 0.87; P-interaction = 0.005). A similar analysis with dietary omega-3 (n-3) PUFAs did not show a statistically significant nutrigenetic association (P-interaction = 0.23). Functional analysis in human aortic endothelial cells showed that the carriers of the G allele had significantly lower PLA2G4A gene expression (P = 0.014), consistent with the atheroprotective association of this variant.These results replicate the association of rs12746200 with CVD phenotypes and provide evidence that the protective association of this functional PLA2G4A variant is mediated by dietary PUFAs.

SUBMITTER: Hartiala J

PROVIDER: S-EPMC3302367 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Association of PLA2G4A with myocardial infarction is modulated by dietary PUFAs.

Hartiala Jaana J Gilliam Elizabeth E Vikman Susanna S Campos Hannia H Allayee Hooman H

The American journal of clinical nutrition 20120229 4

<h4>Background</h4>Leukotrienes are proinflammatory molecules derived from dietary PUFAs and have been associated with cardiovascular disease (CVD). We previously reported that an A→G variant (rs12746200) of the cytosolic phospholipase A2 group IVA gene (PLA2G4A), which encodes the enzyme that liberates PUFAs from cellular membranes for leukotriene synthesis, decreases the risk of CVD.<h4>Objective</h4>We sought to replicate these initial observations with a more clinically relevant phenotype, s ...[more]

PMID: 22378731

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Project description:Diet has been associated with better mental health in general populations, but less is known on this association in patients with a history of coronary heart disease. The objective of this study is to examine the cross-sectional associations between dietary patterns and mental health in elderly patients with a history of myocardial infarction.Data were drawn from the final assessment of the Alpha Omega cohort that monitored patients with a history of myocardial infarction (age range 60-80 years). 2171 patients with complete data for diet and mental health were included in this study. Diet was assessed with the 203-item Food Frequency Questionnaire, and subsequently categorized into two scores: the Dutch Healthy Nutrient and Food Score (DHNaFS) and the Dutch Undesirable Nutrient and Food Score (DUNaFS). Depressive symptoms, assessed with the Geriatric Depression Scale (GDS-15), and dispositional optimism, assessed with the 4-item questionnaire (4Q), were cross-sectionally analyzed in relation to dietary patterns using linear regression analysis.Patients were on average 72.2 years old and 79.5% were male. The DHNaFS score was associated with less depressive symptoms and higher dispositional optimism (? = -0.108; P<0.001; and ? = 0.074; P<0.001), whereas no associations were found with the DUNaFS score. Particularly, consumption of vegetables, fruits, whole grains, fish, and low fat-dairy were associated with less depressive symptoms and higher optimism. Similar associations were found when analyzing the association between average DHNaFS score over the preceding 41 months with depression ? = -0.085; P<0.001) and higher dispositional optimism (? = 0.084; P<0.001).A healthy dietary pattern, in particular a higher consumption of vegetables, fruit, whole grains, fish and low-fat dairy, was associated with less depressive symptoms and higher optimism. However, given the cross-sectional nature of our analyses, our findings may also be explained by more optimistic participants making healthier food choices. Therefore, future prospective or interventions studies are needed to establish the direction of causality of this association.ClinicalTrials.gov NCT03192410.

Project description:BackgroundPreclinical data suggest that an acute inflammatory response following myocardial infarction (MI) accelerates systemic atherosclerosis. Using combined positron emission and computed tomography, we investigated whether this phenomenon occurs in humans.Methods and resultsOverall, 40 patients with MI and 40 with stable angina underwent thoracic 18F-fluorodeoxyglucose combined positron emission and computed tomography scan. Radiotracer uptake was measured in aortic atheroma and nonvascular tissue (paraspinal muscle). In 1003 patients enrolled in the Global Registry of Acute Coronary Events, we assessed whether infarct size predicted early (≤30 days) and late (>30 days) recurrent coronary events. Compared with patients with stable angina, patients with MI had higher aortic 18F-fluorodeoxyglucose uptake (tissue-to-background ratio 2.15±0.30 versus 1.84±0.18, P<0.0001) and plasma C-reactive protein concentrations (6.50 [2.00 to 12.75] versus 2.00 [0.50 to 4.00] mg/dL, P=0.0005) despite having similar aortic (P=0.12) and less coronary (P=0.006) atherosclerotic burden and similar paraspinal muscular 18F-fluorodeoxyglucose uptake (P=0.52). Patients with ST-segment elevation MI had larger infarcts (peak plasma troponin 32 300 [10 200 to >50 000] versus 3800 [1000 to 9200] ng/L, P<0.0001) and greater aortic 18F-fluorodeoxyglucose uptake (2.24±0.32 versus 2.02±0.21, P=0.03) than those with non-ST-segment elevation MI. Peak plasma troponin concentrations correlated with aortic 18F-fluorodeoxyglucose uptake (r=0.43, P=0.01) and, on multivariate analysis, independently predicted early (tertile 3 versus tertile 1: relative risk 4.40 [95% CI 1.90 to 10.19], P=0.001), but not late, recurrent MI.ConclusionsThe presence and extent of MI is associated with increased aortic atherosclerotic inflammation and early recurrent MI. This finding supports the hypothesis that acute MI exacerbates systemic atherosclerotic inflammation and remote plaque destabilization: MI begets MI.Clinical trial registrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT01749254.

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Association of PLA2G4A with myocardial infarction is modulated by dietary PUFAs.

Publications

Association of PLA2G4A with myocardial infarction is modulated by dietary PUFAs.

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