P1748TNF and ANXA2 gene polymorphism associated with outcome and coronary angiography features in patients with early acute coronary syndrome (original) (raw)
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Tumor necrosis factor receptor 2 gene (TNFRSF1B) in genetic basis of coronary artery disease
Journal of Molecular Medicine, 2001
Tumor necrosis factor (TNF)-α has been implicated in pathophysiological processes in coronary artery disease (CAD). TNF receptor 2 is of particular interest in mediating such effects. The gene for this receptor (TNF-RSF1B) has, moreover, been implicated in hypertension, elevated cholesterol and insulin resistance. TNFRSF1B is thus a worthy candidate in studies of the genetic basis of CAD. We therefore conducted a case-control study of a microsatellite marker with five alleles (CA13-CA17) in intron 4 of TNFRSF1B in 1006 well-characterized white patients with angiographically confirmed CAD and a control group of 183 healthy subjects. We found a strong association of the TNFRSF1B marker with CAD (χ 2 =40, P=0.00000069). The frequency of the CA16 allele was 33% in CAD vs. 21% in control (odds ratio, OR, to have CAD for presence vs. absence of CA16 allele in CA16 homozygotes was 4.5, 95% CI 2.1-9.4, P<0.0001; in CA16 heterozygotes OR was 1.3, 95% CI 0.94-1.89, P=0.10). The frequency of the major allele (CA15) was 43% in CAD vs. 56% in controls (in CA15 homozygotes OR 0.33, 95% CI 0.20-0.52, P<0.0001; in heterozygotes OR 0.41, 95% CI 0.26-0.63, P<0.0001). In a stepwise logistic regression model the CA16 allele was significantly associated with overweight (OR 1.44, 95% CI 1.0-1.9, P=0.027). Apolipoprotein A-I was elevated (P<0.0001), as was high-density lipoprotein (P=0.098), and severity of angina was decreased (P=0.024) as a function of genotype. Plasma soluble (s) TNF-R2 was 5.1±0.1 ng/ml in CAD vs. 3.2±0.1 in control (P<0.0001), 5.2±0.1 in the presence vs. 4.6±0.2 in the absence of vessel disease (P=0.009), and rose with increasing severity of angina: 4.2±0.2 (no angina), 5.0±0.1 (stable angina), 5.4±0.2 (unstable angina; P=0.003). sTNF-R2 was correlated with age, cholesterol, creatinine, fibrinogen, transforming growth factor β and homocysteine and was influenced by TNFRSF1B genotype. Thus genetic variation in or near the TNFRSF1B locus may predispose to CAD.
Genetics in Medicine, 2005
for the CARDIOGENE Study group Purpose: We investigated the association of a polymorphism within the promoter of ⌻⌵F-␣ locus at the position Ϫ308 on the likelihood of having acute coronary syndromes (ACS) in Greek adults. Methods: We studied demographic, lifestyle, and clinical information in 237 hospitalized patients (185 males) with a first event of an ACS and 237 matched by age and sex (controls) without any clinical evidence of coronary heart disease. Genotyping was performed by PCR-RFLP analysis. Results: The genotype frequencies were in patients, 87% (n ϭ 206), 12% (n ϭ 29), and 1% (n ϭ 2
The –308 G/A Tumor Necrosis Factor-α Gene Dimorphism: A Risk Factor for Unstable Angina
Clinical Chemistry and Laboratory Medicine, 2003
Since the inflammatory cytokine tumor necrosis factor-␣ (TNF-␣) may play a major role in the pathophysiology of acute coronary syndromes, 299 consecutive male patients hospitalized for coronary artery disease (i.e., lumen lost ≥ 50%) were genotyped for the functional-308G/A TNF-␣ polymorphism using restriction fragment length polymorphism method, in order to evaluate its potential association with the risk of unstable angina and/or myocardial infarction. A higher frequency of carriers of the A allele was observed in patients with unstable angina (n = 58) when compared to control patients with stable angina (n = 95) (39.66% vs. 23.16% respectively, p = 0.029, odds ratio = 2.2) but not in patients with myocardial infarction (n = 146) (23.97% vs. 23.16%, p = NS). Furthermore, we evidenced an interaction of the polymorphism studied with body mass index in patients with unstable angina. Thus, when stratified analysis was performed, results in patients with a body mass index ≤ 27 showed a more striking association between A allele carriage frequency and unstable angina (p = 0.012, odds ratio = 3.0). These results suggest the crucial role of TNF-␣ in the mechanisms responsible for unstable angina in accordance with the concept of vulnerable plaque. On the other hand, mechanisms controlling myocardial infarction appear more complex and heterogeneous.
Genetics in Medicine, 2005
for the CARDIOGENE Study group Purpose: We investigated the association of a polymorphism within the promoter of ⌻⌵F-␣ locus at the position Ϫ308 on the likelihood of having acute coronary syndromes (ACS) in Greek adults. Methods: We studied demographic, lifestyle, and clinical information in 237 hospitalized patients (185 males) with a first event of an ACS and 237 matched by age and sex (controls) without any clinical evidence of coronary heart disease. Genotyping was performed by PCR-RFLP analysis. Results: The genotype frequencies were in patients, 87% (n ϭ 206), 12% (n ϭ 29), and 1% (n ϭ 2
Role of Cytokine Gene Score in Risk Prediction of Premature Coronary Artery Disease
Genetic testing and molecular biomarkers, 2016
Pro- and anti-inflammatory cytokines play a significant role in early atherosclerosis. Linkage disequilibrium patterns differ between ethnic groups pointing toward the need to develop population-specific gene risk scores. Our objective was to investigate the role of a cytokine gene score in the risk prediction of premature coronary artery disease (PCAD). A case-control study was performed at the National University of Sciences and Technology (NUST) in collaboration with the Cardiovascular Genetics Institute, University College London, United Kingdom. Three hundred forty subjects with >70% stenosis in at least one coronary vessel on angiography were labeled as PCAD cases and compared with 310 angio-negative controls. Genotyping of the rs187238 (interleukin [IL]-18), rs1800795 (IL-6), rs1800629 (tumor necrosis factor [TNF]-alpha), rs1800871 (IL-10), and rs1946519 (IL-18) SNPs was performed using KASPar and TaqMan assays. The odds ratio for cytokine gene score was significantly high...
The -308 G/A tumor necrosis factor-alpha gene dimorphism: a risk factor for unstable angina
Clinical chemistry and laboratory medicine : CCLM / FESCC, 2003
Since the inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) may play a major role in the pathophysiology of acute coronary syndromes, 299 consecutive male patients hospitalized for coronary artery disease (i.e., lumen lost > or = 50%) were genotyped for the functional -308G/A TNF-alpha polymorphism using restriction fragment length polymorphism method, in order to evaluate its potential association with the risk of unstable angina and/or myocardial infarction. A higher frequency of carriers of the A allele was observed in patients with unstable angina (n = 58) when compared to control patients with stable angina (n = 95) (39.66% vs. 23.16% respectively, p = 0.029, odds ratio = 2.2) but not in patients with myocardial infarction (n = 146) (23.97% vs. 23.16%, p = NS). Furthermore, we evidenced an interaction of the polymorphism studied with body mass index in patients with unstable angina. Thus, when stratified analysis was performed, results in patients with a body mas...
Gene Polymorphisms in the TNF Locus and the Risk of Myocardial Infarction
Thrombosis Research, 2000
of polymorphisms in the TNF locus with major risk factors for CAD may exist, and should be explored We investigated two genetic polymorphisms in the in larger studies. © 2000 Elsevier Science Ltd. All tumor necrosis factor locus (TNF-␣ Ϫ308 G→A rights reserved. and LT-␣ ϩ252 A→G) as risk factors for coronary atherothrombotic disease (CAD) by determining its prevalence in 148 survivors of myocardial in-
Arteriosclerosis, Thrombosis, and Vascular Biology, 2005
Objective-Tissue factor (TF) has, among other factors, a prominent role in acute coronary syndrome (ACS). Our goal was to investigate whether single nucleotide polymorphisms (SNP) in the TF gene (F3) are associated with plasma TF, risk, and outcome in patients with ACS. Moreover, we wanted to investigate the impact of associated TF SNPs on mRNA production in human monocytes. Methods and Results-In 725 patients with ACS [Fragmin and Fast Revascularization during Instability in Coronary Artery Disease II (FRISC-II) study] and 376 controls, 13 SNPs were genotyped and plasma TF measured. Thereafter, the 5466 AϾG and the Ϫ1812 CϾT were genotyped among all of the FRISC-II participants (nϭ3143) and assessed concerning clinical outcome. Associated SNPs were genotyped in 92 healthy blood donors for comparison of TF activity and TF mRNA expression. None of the SNPs were associated with patient/control status. The 5466 AϾG SNP was associated with cardiovascular death (odds ratio, 1.8; Pϭ0.025). The CG haplotype by Ϫ1812 CϾT and 5466 AϾG was associated with a 3-fold increased risk of death (PϽ0.001). TF mRNA and basal TF activity was significantly lower among 5466 AG carriers, whereas the increase in monocyte TF activity on lipopolysaccharide stimulation was significantly stronger (Pϭ0.04). Conclusions-The 5466 AG genotype is a novel predictor of cardiovascular death in ACS and may act through a high TF response.
Association of TNF-α serum levels and TNFA promoter polymorphisms with risk of myocardial infarction
Atherosclerosis, 2006
Elevated levels of tumor necrosis factor-alpha (TNF-␣), and presence of polymorphisms of the TNFA gene have been implicated in cardiovascular disease pathogenesis. We explored the relationship between polymorphisms in the TNFA gene (−1031C/T, −863C/A −857T/C, −308G/A, −238G/A), protein levels of TNF-␣ and their association to myocardial infarction (MI) using a sample of 1213 post-MI patients and 1561 healthy controls. MI risk was higher among men with elevated TNF-␣ levels, with the highest compared to the lowest TNF-␣ quartile giving a 70% risk increase (OR [95% CI]: 1.7 [1.1; 2.6]). Obese subjects who also had elevated TNF-␣ levels were at even higher risk for MI (OR [95% CI]: 3.4 [2.1; 5.6]). Higher TNF-␣ levels were seen among smokers (but not among non-smokers) carrying the −857T allele. Furthermore, a rare haplotype occurred more frequently among the cases than the controls. Elevated TNF-␣ levels are associated with increased MI risk. Obese subjects with elevated TNF-a levels, and carriers of polymorphisms in or near TNFA are particularly susceptible to the hazards of smoking, results which may have implications for cardiovascular preventive measures.