Prediction of the Risk of Myocardial Infarction from Polymorphisms in Candidate Genes

Yamada, Yoshiji; Izawa, Hideo; Ichihara, Sahoko; Takatsu, Fumimaro; Ichikawa, Hitoshi; Hanawa, Haruo; Sone, Toshio; Tanaka, Masashi; Yokota, Mitsuhiro

doi:10.1056/nejmoa021445

Cited by 582 publications

(198 citation statements)

References 20 publications

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“…[4][5][6][7][8] Recently, genetic risk scores (GRSs) for CAD, consisting of specific genetic variants identified from genome-wide association studies, have also been associated with incident cardiovascular disease and have shown promise in improving cardiovascular risk prediction. [9][10][11][12][13][14][15][16][17][18][19][20][21][22] However, the exact predisposing mechanisms that account for the increased risk in patients with a FHx or a high GRS remain unclear.…”

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confidence: 99%

Association Between Family History, a Genetic Risk Score, and Severity of Coronary Artery Disease in Patients With Premature Acute Coronary Syndromes

Hindieh

Pilote

Cheema

et al. 2016

ATVB

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Objective-A genetic risk score (GRS) for coronary artery disease has recently been shown to be independent of family history (FHx) in predicting future cardiovascular events. We sought to determine whether the presence of these risk factors, either individually or together, was associated with a higher burden of angiographic coronary artery disease. Approach and Results-We included 763 patients with premature acute coronary syndrome (median age, 50 [46-53] years; 30.8% women) with at least 1 major epicardial vessel stenosis enrolled in the Gender and Sex Determinants of Cardiovascular Disease From Bench to Beyond in Premature Acute Coronary Syndrome (GENESIS-PRAXY) study, a multicentre prospective cohort study of premature patients with acute coronary syndrome (aged ≤55 years). Key Words: acute coronary syndrome ◼ atherosclerosis ◼ cohort studies ◼ coronary heart disease ◼ genetics ◼ myocardial infarction

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confidence: 99%

Association Between Family History, a Genetic Risk Score, and Severity of Coronary Artery Disease in Patients With Premature Acute Coronary Syndromes

Hindieh

Pilote

Cheema

et al. 2016

ATVB

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“…Recent genetic association studies link the thrombospondin (TSP) 2 protein family to the development of atherosclerotic lesions (3)(4)(5)(6)(7)(8)(9)(10). TSP-1 was found in early atherosclerotic lesions (11), in injured vascular walls (12,13), and in cardiac allografts where its expression correlated with the degree of vasculopathy (14).…”

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Glycosylation Mediates Up-regulation of a Potent Antiangiogenic and Proatherogenic Protein, Thrombospondin-1, by Glucose in Vascular Smooth Muscle Cells

Raman

Krukovets

Marinic

et al. 2007

Journal of Biological Chemistry

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Thrombospondins are matricellular proteins that regulate cell-cell and cell-matrix interactions (1, 2). Recent genetic association studies link the thrombospondin (TSP) 2 protein family to the development of atherosclerotic lesions (3-10). TSP-1 was found in early atherosclerotic lesions (11), in injured vascular walls (12,13), and in cardiac allografts where its expression correlated with the degree of vasculopathy (14). The genetic disruption of TSP-1 reduced the atherosclerotic lesion area in the mouse model of atherosclerosis and suggested an important role for TSP-1 in the evolution of plaque and its composition (15). In both in vivo and in vitro studies TSP-1 induced proliferation of vascular smooth muscle cells (SMC) (16,17), and both TSP-1 and TSP-2 inhibited growth of endothelial cells (18 -21); both effects are considered proatherogenic.Previous studies have documented increased TSP-1 levels in the plasma and kidneys of diabetic patients and diabetic animal models (22-25). In mesangial cells, the level of TSP-1 was upregulated by glucose by a transcriptional mechanism (26 -28). We have recently reported increased levels of TSP-1 in the blood vessels of diabetic animals (29). Moreover, TSP-1 was up-regulated by high glucose in vitro in major cell types from large blood vessels. These observations suggest that TSP-1 represents an important link between diabetes, hyperglycemia, and accelerated atherogenesis.A large number of clinical studies and trials have conclusively identified hyperglycemia as an independent risk factor for development of both micro-and macrovascular complications (30 -33). Recently, the Epidemiology of Diabetes Intervention and Complications study reported that, as compared with conventional therapy, intensive glycemic control reduced the risk of the most serious cardiovascular events such as heart attacks, stroke, and death by nearly 60%. These findings clearly underscore the importance of hyperglycemia as a critical player in the development of pathogenic complications associated with diabetes. Glucose regulates the expression of a number of vascular * This work was supported by National Institutes of Health Grants R01 DK067532, K01 DK62128, and P50 HL077107, American Heart Association Grant 0565284B, and funds from the Lerner Research Institute (Cleveland Clinic) (to O. I. S.) and by National Institutes of Health Grant R01 45418 (to P. B.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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“…The TSP-1 SNP is a rare N700S recessive trait (1% frequency) but has the highest association with disease (odds ratio for MI ϭ 8.66). This rarity leads to a low likelihood of successful replication in small studies (7,8), but in one subsequent preliminary report (9) this disease association of the Ser-700 variant was corroborated.…”

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Molecular and Functional Differences Induced in Thrombospondin-1 by the Single Nucleotide Polymorphism Associated with the Risk of Premature, Familial Myocardial Infarction

Narizhneva

Byers-Ward

Quinn

et al. 2004

Journal of Biological Chemistry

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A serine (Ser-700) amino acid rather than an asparagine (Asn-700) at residue 700 of thrombospondin-1 has been linked to an increased risk for development of premature, familial heart attacks. We now have identified both functional and structural differences between the Ser-700 and Asn-700 thrombospondin-1 variants. The Ser-700 variant increased the rate and extent of platelet aggregation and showed increased surface expression on platelets compared with the Asn-700 variant. These differences could be ascribed to an enhanced interaction of the Ser-700 variant with fibrinogen on the platelet surface and are consistent with a prothrombotic phenotype in Ser-700 individuals. The Ser-700 variant thrombospondin-1 was conformationally more labile than the Asn-700 variant as demonstrated by increased susceptibility to proteolytic digestion and enhanced susceptibility to unfolding by denaturants. These data suggest a potential molecular and cellular basis for a genetic risk factor associated with early onset myocardial infarction.

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Prediction of the Risk of Myocardial Infarction from Polymorphisms in Candidate Genes

Abstract: Determination of the genotypes of the connexin 37, plasminogen-activator inhibitor type 1, and stromelysin-1 genes may prove reliable in predicting the genetic risk of myocardial infarction and might thus contribute to the primary prevention of this condition.

Cited by 582 publications

References 20 publications

Association Between Family History, a Genetic Risk Score, and Severity of Coronary Artery Disease in Patients With Premature Acute Coronary Syndromes

Association Between Family History, a Genetic Risk Score, and Severity of Coronary Artery Disease in Patients With Premature Acute Coronary Syndromes

Glycosylation Mediates Up-regulation of a Potent Antiangiogenic and Proatherogenic Protein, Thrombospondin-1, by Glucose in Vascular Smooth Muscle Cells

Molecular and Functional Differences Induced in Thrombospondin-1 by the Single Nucleotide Polymorphism Associated with the Risk of Premature, Familial Myocardial Infarction

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