Dataset Information

E-selectin gene haplotypes are associated with the risk of myocardial infarction.

ABSTRACT: Introduction:Endothelial dysfunction is one of the most important factors implicated in the pathogenesis of coronary artery disease (CAD). The aim of this study was to investigate the association of the E-selectin gene (SELE) with CAD and CAD-related traits using tagging polymorphisms. Material and methods:A total of 379 Polish patients who had undergone angiography were included: 261 patients with angiographically documented CAD, 202 CAD patients without myocardial infarction (CAD/MI(-) group) and 59 patients with myocardial infarction (CAD/MI(+) group) as well as 118 healthy control subjects (non-CAD). Eight tagging single nucleotide polymorphisms (SNPs) in the SELE gene were selected using genotype data from HapMap. Genotyping was performed using PCR-RFLP and PCR-DHPLC methods. Results:The most common SELE haplotype in this analysis ([C;G;T;C;G;T], 31.2%) showed a negative association with myocardial infarction (MI) (CAD/MI(+) vs. non-CAD) under the additive (p = 0.001), dominant (p = 0.006) and recessive (p = 0.012) model. Two other haplotypes ([C;G;C;C;A;C], [C;A;C;A;G;T], 5.73% and 18.1%, respectively) were also negatively associated with MI under the additive and dominant model. We also found two haplotypes ([T;G;T;C;G;T], [C;G;C;C;A;T], 1.52% and 6.71%, respectively) associated with the risk for MI (CAD/MI(+) vs. CAD/MI(-)), acting in both additive (p = 0.04, p = 0.007, respectively) and dominant (p = 0.04, p = 0.004, respectively) manner. There was no association with either CAD/MI(-) or with severity of CAD expressed as the number of vessels involved. Conclusions:Our results suggest that SELE is one of the independent genetic factors modifying the risk of myocardial infarction.

SUBMITTER: Goracy J

PROVIDER: S-EPMC6764297 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

E-selectin gene haplotypes are associated with the risk of myocardial infarction.

Gorący Jarosław J Kaczmarczyk Mariusz M Ciechanowicz Andrzej A Safranow Krzysztof K Gorący Joanna J Jakubowska Katarzyna K Chlubek Dariusz D Gorący Iwona I

Archives of medical science : AMS 20190409 5

<h4>Introduction</h4>Endothelial dysfunction is one of the most important factors implicated in the pathogenesis of coronary artery disease (CAD). The aim of this study was to investigate the association of the E-selectin gene (<i>SELE</i>) with CAD and CAD-related traits using tagging polymorphisms.<h4>Material and methods</h4>A total of 379 Polish patients who had undergone angiography were included: 261 patients with angiographically documented CAD, 202 CAD patients without myocardial infarct ...[more]

PMID: 31572467

Similar Datasets

Project description:BackgroundGenetic risk scores have been developed for coronary artery disease and atherosclerosis, but are not predictive of adverse cardiovascular events. We asked whether peripheral blood expression profiles may be predictive of acute myocardial infarction (AMI) and/or cardiovascular death.MethodsPeripheral blood samples from 338 subjects aged 62 ± 11 years with coronary artery disease (CAD) were analyzed in two phases (discovery N = 175, and replication N = 163), and followed for a mean 2.4 years for cardiovascular death. Gene expression was measured on Illumina HT-12 microarrays with two different normalization procedures to control technical and biological covariates. Whole genome genotyping was used to support comparative genome-wide association studies of gene expression. Analysis of variance was combined with receiver operating curve and survival analysis to define a transcriptional signature of cardiovascular death.ResultsIn both phases, there was significant differential expression between healthy and AMI groups with overall down-regulation of genes involved in T-lymphocyte signaling and up-regulation of inflammatory genes. Expression quantitative trait loci analysis provided evidence for altered local genetic regulation of transcript abundance in AMI samples. On follow-up there were 31 cardiovascular deaths. A principal component (PC1) score capturing covariance of 238 genes that were differentially expressed between deceased and survivors in the discovery phase significantly predicted risk of cardiovascular death in the replication and combined samples (hazard ratio = 8.5, P < 0.0001) and improved the C-statistic (area under the curve 0.82 to 0.91, P = 0.03) after adjustment for traditional covariates.ConclusionsA specific blood gene expression profile is associated with a significant risk of death in Caucasian subjects with CAD. This comprises a subset of transcripts that are also altered in expression during acute myocardial infarction.

Project description:DNA methylation profiles are responsive to environmental stimuli and metabolic shifts. This makes DNA methylation a potential biomarker of environmental-related and lifestyle-driven diseases of adulthood. Therefore, we investigated if white blood cells' (WBCs) DNA methylation profiles are associated with myocardial infarction (MI) occurrence. Whole-genome DNA methylation was investigated by microarray analysis in 292 MI cases and 292 matched controls from the large prospective Italian European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (EPICOR study). Significant signals (false discovery rate (FDR) adjusted P?<?0.05) were replicated by mass spectrometry in 317 MI cases and 262 controls from the Dutch EPIC cohort (EPIC-NL). Long interspersed nuclear element-1 (LINE-1) methylation profiles were also evaluated in both groups.A differentially methylated region (DMR) within the zinc finger and BTB domain-containing protein 12 (ZBTB12) gene body and LINE-1 hypomethylation were identified in EPICOR MI cases and replicated in the EPIC-NL sample (ZBTB12-DMR meta-analysis: effect size?±?se?=?-0.016?±?0.003, 95 % CI?=?-0.021;-0.011, P?=?7.54?×?10(-10); LINE-1 methylation meta-analysis: effect size?±?se?=?-0.161?±?0.040, 95 % CI?=?-0.239;-0.082, P?=?6.01?×?10(-5)). Moreover, cases with shorter time to disease had more pronounced ZBTB12-DMR hypomethylation (meta-analysis, men: effect size?±?se?=?-0.0059?±?0.0017, P TREND?=?5.0?×?10(-4); women: effect size?±?se?=?-0.0053?±?0.0019, P TREND?=?6.5?×?10(-3)) and LINE-1 hypomethylation (meta-analysis, men: effect size?±?se?=?-0.0010?±?0.0003, P TREND?=?1.6?×?10(-3); women: effect size?±?se?=?-0.0008?±?0.0004, P TREND?=?0.026) than MI cases with longer time to disease. In the EPIC-NL replication panel, DNA methylation profiles improved case-control discrimination and reclassification when compared with traditional MI risk factors only (net reclassification improvement (95 % CI) between 0.23 (0.02-0.43), P?=?0.034, and 0.89 (0.64-1.14), P?<?1?×?10(-5)).Our data suggest that specific methylation profiles can be detected in WBCs, in a preclinical condition, several years before the occurrence of MI, providing an independent signature of cardiovascular risk. We showed that prediction accuracy can be improved when DNA methylation is taken into account together with traditional MI risk factors, although further confirmation on a larger sample is warranted. Our findings support the potential use of DNA methylation patterns in peripheral blood white cells as promising early biomarkers of MI.

Project description:OBJECTIVE:P-selectin (PSEL) and its ligand, P-selectin glycoprotein ligand-1 (PSGL-1), play key roles in both the inflammatory response and the atherosclerotic process, but there are conflicting results regarding the affect of PSEL and PSGL-1 gene variation on risk for cardiovascular and cerebrovascular disease. We tested the association of four PSEL and two PSGL-1 polymorphisms with incident coronary heart disease (CHD) and ischemic stroke among 13,875 participants in the prospective Atherosclerosis Risk in Communities (ARIC) study. We also tested common haplotypes in the PSEL and PSGL-1 genes to assess associations with incident CHD and ischemic stroke. METHODS AND RESULTS:Incident ischemic stroke and CHD were identified through annual telephone calls and hospital and death certificate surveillance. Five hundred and twenty-five validated ischemic stroke and 1654 CHD events were identified. Allele frequencies for all PSEL and PSGL-1 polymorphisms were markedly different between whites and African Americans; therefore, all analyses were performed race-specific. Independent analyses showed the PSEL 290NN genotype to be a significant predictor of CHD in whites (HRR 1.30, 95%CI 1.00-1.70, P=0.05). PSGL-1 genotypes carrying the 62I allele were significantly protective for incident CHD (HRR 0.53, 95%CI 0.31-0.92, P=0.02) and ischemic stroke (HRR 0.73, 95%CI 0.55-0.97, P=0.03) in African Americans. Haplotype analyses showed the PSEL NNVP haplotype to be a significant predictor of incident CHD in whites (HRR 2.09, 95%CI 1.23-3.55, P=0.006). No significant haplotype findings were observed in African Americans. CONCLUSIONS:PSEL S290N, in single polymorphism analysis and in the haplotypic background with T715P, was associated with increased risk of incident CHD in whites. The PSGL-1 M62I polymorphism was associated with decreased risk of both incident CHD and stroke in African Americans. These findings illustrate the complex relationship between genetic variation and disease in different racial groups.

Dataset Information

E-selectin gene haplotypes are associated with the risk of myocardial infarction.

Publications

E-selectin gene haplotypes are associated with the risk of myocardial infarction.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets