Dataset Information

Six sequence variants on chromosome 9p21.3 are associated with a positive family history of myocardial infarction: a multicenter registry.

ABSTRACT: BACKGROUND: Recent genome-wide association studies have identified several genetic loci linked to coronary artery disease (CAD) and myocardial infarction (MI). The 9p21.3 locus was verified by numerous replication studies to be the first common locus for CAD and MI. In the present study, we investigated whether six single nucleotide polymorphisms (SNP) rs1333049, rs1333040, rs10757274, rs2383206, rs10757278, and rs2383207 representing the 9p21.3 locus were associated with the incidence of an acute MI in patients with the main focus on the familial aggregation of the disease. METHODS: The overall cohort consisted of 976 unrelated male patients presenting with an acute coronary syndrome (ACS) with ST-elevated (STEMI) as well as non-ST-elevated myocardial infarction (NSTEMI). Genotyping data of the investigated SNPs were generated and statistically analyzed in comparison to previously published findings of matchable control cohorts. RESULTS: Statistical evaluation confirmed a highly significant association of all analyzed SNP's with the occurrence of MI (p<0.0001; OR: 1.621-2.039). When only MI patients with a positive family disposition were comprised in the analysis a much stronger association of the accordant risk alleles with incident disease was found with odds ratios up to 2.769. CONCLUSIONS: The findings in the present study confirmed a strong association of the 9p21.3 locus with MI particularly in patients with a positive family history thereby, emphasizing the pathogenic relevance of this locus as a common genetic cardiovascular risk factor.

SUBMITTER: Scheffold T

PROVIDER: S-EPMC3061953 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Six sequence variants on chromosome 9p21.3 are associated with a positive family history of myocardial infarction: a multicenter registry.

Scheffold Thomas T Kullmann Silke S Huge Andreas A Binner Priska P Ochs Hermann R HR Schöls Wolfgang W Thale Joachim J Motz Wolfgang W Hegge Franz Josef FJ Stellbrink Christoph C Dorsel Thomas T Gülker Hartmut H Heuer Hubertus H Dinh Wilfried W Stoll Monika M Haltern Georg G

BMC cardiovascular disorders 20110307

<h4>Background</h4>Recent genome-wide association studies have identified several genetic loci linked to coronary artery disease (CAD) and myocardial infarction (MI). The 9p21.3 locus was verified by numerous replication studies to be the first common locus for CAD and MI. In the present study, we investigated whether six single nucleotide polymorphisms (SNP) rs1333049, rs1333040, rs10757274, rs2383206, rs10757278, and rs2383207 representing the 9p21.3 locus were associated with the incidence of ...[more]

PMID: 21385355

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Project description:BackgroundWe aimed to describe the characteristics and in-hospital outcomes of ST-segment elevation myocardial infarction (STEMI) patients during the Covid-19 era.MethodsWe conducted a prospective, multicenter study involving 13 intensive cardiac care units, to evaluate consecutive STEMI patients admitted throughout an 8-week period during the Covid-19 outbreak. These patients were compared with consecutive STEMI patients admitted during the corresponding period in 2018 who had been prospectively documented in the Israeli bi-annual National Acute Coronary Syndrome Survey. The primary end-point was defined as a composite of malignant arrhythmia, congestive heart failure, and/or in-hospital mortality. Secondary outcomes included individual components of primary outcome, cardiogenic shock, mechanical complications, electrical complications, re-infarction, stroke, and pericarditis.ResultsThe study cohort comprised 1466 consecutive acute MI patients, of whom 774 (53%) were hospitalized during the Covid-19 outbreak. Overall, 841 patients were diagnosed with STEMI: 424 (50.4%) during the Covid-19 era and 417 (49.6%) during the parallel period in 2018. Although STEMI patients admitted during the Covid-19 period had fewer co-morbidities, they presented with a higher Killip class (p value = .03). The median time from symptom onset to reperfusion was extended from 180 minutes (IQR 122-292) in 2018 to 290 minutes (IQR 161-1080, p < .001) in 2020. Hospitalization during the Covid-19 era was independently associated with an increased risk of the combined endpoint in the multivariable regression model (OR 1.65, 95% CI 1.03-2.68, p value = .04). Furthermore, the rate of mechanical complications was four times higher during the Covid-19 era (95% CI 1.42-14.8, p-value = .02). However, in-hospital mortality remained unchanged (OR 1.73, 95% CI 0.81-3.78, p-value = .16).ConclusionsSTEMI patients admitted during the first wave of Covid-19 outbreak, experienced longer total ischemic time, which was translated into a more severe disease status upon hospital admission, and a higher rate of in-hospital adverse events, compared with parallel period.

Project description:BACKGROUND: Genetic variation at 1p13 modulates serum lipid levels and the risk of coronary heart disease through the regulation of serum lipid levels. Here we investigate if the interaction between genetic variants at 1p13 and serum lipid levels affects the risk of non-fatal myocardial infarction (MI) in the Stockholm Heart Epidemiology Program (SHEEP), a large population based case control study. METHODS: In the present study only non fatal MI cases (n?=?1213, men/women: 852/361) and controls (n?=?1516, men/women =1054/507) matched by age, sex and residential area, were included. Three SNPs 12740374?G/T, rs599839A/G and rs646776T/C mapping at 1p13 were analysed for association with serum lipid levels and the risk of MI by a weighted least square regression and logistic regression analyses, respectively. To analyse the effect of the interaction between genetic variants and serum lipid levels on the risk of MI, we applied the biological model of interaction that estimates the difference in risk, expressed as OR (95%CI), observed in the presence and in the absence of both exposures. One derived measure is the Synergy index (S) and 95%CI, where S?>?1 indicates synergy and S?<?1 antagonism between the two interaction terms. RESULTS: Rs12740374G/T and rs646776T/C were in strong linkage disequilibrium (LD) (r2?=?0.99), therefore only rs599839A/G and rs646776 were included in the analysis. Consistently with published data, presence of the rare genotypes was associated with reduced total-, LDL-cholesterol and ApoB serum levels (all p?<?0.05) as compared to the reference genotype, but was not associated with the risk of MI.However, the increased risk of MI observed in individual exposed to high (?75th percentile) serum lipid levels was offset in subjects carrying the rare alleles G and C. In particular, the risk of MI associated with high ApoB serum levels OR (95%CI) 2.27 (1.86-2.77) was reduced to 1.76 (1.33-2.34) in the presence of the G allele at rs599839 with an S of 0.47 (0.20-0.90). CONCLUSIONS: These results indicate that an antagonism between ApoB serum levels and genetic variants at 1p13 contributes to reduce the risk of non-fatal MI in the presence of high ApoB serum levels.

Dataset Information

Six sequence variants on chromosome 9p21.3 are associated with a positive family history of myocardial infarction: a multicenter registry.

Publications

Six sequence variants on chromosome 9p21.3 are associated with a positive family history of myocardial infarction: a multicenter registry.

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