Homocysteine concentration in coronary artery disease: Influence of three common single nucleotide polymorphisms
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Homocysteine concentration in coronary artery disease: Influence of three common single nucleotide polymorphisms. / Bickel, C; Schnabel, R B; Zengin, E; Lubos, E; Rupprecht, H; Lackner, K; Proust, C; Tregouet, D; Blankenberg, S; Westermann, D; Sinning, C.
in: NUTR METAB CARDIOVAS, Jahrgang 27, Nr. 2, 02.2017, S. 168-175.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Homocysteine concentration in coronary artery disease: Influence of three common single nucleotide polymorphisms
AU - Bickel, C
AU - Schnabel, R B
AU - Zengin, E
AU - Lubos, E
AU - Rupprecht, H
AU - Lackner, K
AU - Proust, C
AU - Tregouet, D
AU - Blankenberg, S
AU - Westermann, D
AU - Sinning, C
N1 - Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
PY - 2017/2
Y1 - 2017/2
N2 - BACKGROUND AND AIMS: Whether single nucleotide polymorphisms (SNPs) of homocysteine metabolism enzymes influence the rate of cardiovascular (CV) events in coronary artery disease (CAD) patients remains controversial.METHODS AND RESULTS: In this analysis, 1126 subjects from the AtheroGene study with CAD and 332 control subjects without known CAD were included. The following SNPs were investigated: methylentetrahydrofolate reductase (MTHFR-C667T), methionin synthetase (MS-D919G), and cystathionin beta synthetase (CBS-I278T). The endpoint was the combination of cardiovascular death, stroke, and non-fatal myocardial infarction (N = 286). The median follow-up time was 6.4 years. Kaplan-Meier curve analysis showed an increasing event rate with rising homocysteine levels (p < 0.001) in CAD patients. Further, in Cox-Regression analysis homocysteine was a predictor of the endpoint with a hazard ratio (HR) of 6.5 (95% CI: 2.9-14.6, p < 0.001) in the adjusted model including cardiovascular risk factors. Of the three SNPs, homozygous MTHFR SNP increased homocysteine levels significantly in patients with CAD and individuals without CAD (both p < 0.001). The SNPs in MS and CBS were not related to relevant changes in homocysteine levels in CAD patients or controls. The different SNPs of MTHFR, MS, and CBS were not related to an increased event rate.CONCLUSION: Homocysteine level is a strong predictor of CV events. Subjects with and without CAD and SNPs in the enzyme MTHFR had increased homocysteine levels. This was not observed for MS and CBS SNPs. Although MTHFR SNPs alter homocysteine levels in patients and controls, these polymorphisms had no impact on prognosis in CAD patients.
AB - BACKGROUND AND AIMS: Whether single nucleotide polymorphisms (SNPs) of homocysteine metabolism enzymes influence the rate of cardiovascular (CV) events in coronary artery disease (CAD) patients remains controversial.METHODS AND RESULTS: In this analysis, 1126 subjects from the AtheroGene study with CAD and 332 control subjects without known CAD were included. The following SNPs were investigated: methylentetrahydrofolate reductase (MTHFR-C667T), methionin synthetase (MS-D919G), and cystathionin beta synthetase (CBS-I278T). The endpoint was the combination of cardiovascular death, stroke, and non-fatal myocardial infarction (N = 286). The median follow-up time was 6.4 years. Kaplan-Meier curve analysis showed an increasing event rate with rising homocysteine levels (p < 0.001) in CAD patients. Further, in Cox-Regression analysis homocysteine was a predictor of the endpoint with a hazard ratio (HR) of 6.5 (95% CI: 2.9-14.6, p < 0.001) in the adjusted model including cardiovascular risk factors. Of the three SNPs, homozygous MTHFR SNP increased homocysteine levels significantly in patients with CAD and individuals without CAD (both p < 0.001). The SNPs in MS and CBS were not related to relevant changes in homocysteine levels in CAD patients or controls. The different SNPs of MTHFR, MS, and CBS were not related to an increased event rate.CONCLUSION: Homocysteine level is a strong predictor of CV events. Subjects with and without CAD and SNPs in the enzyme MTHFR had increased homocysteine levels. This was not observed for MS and CBS SNPs. Although MTHFR SNPs alter homocysteine levels in patients and controls, these polymorphisms had no impact on prognosis in CAD patients.
KW - 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase/genetics
KW - Aged
KW - Area Under Curve
KW - Biomarkers/blood
KW - Case-Control Studies
KW - Chi-Square Distribution
KW - Coronary Artery Disease/blood
KW - Cystathionine beta-Synthase/genetics
KW - Disease Progression
KW - Female
KW - Gene Frequency
KW - Genetic Association Studies
KW - Genetic Predisposition to Disease
KW - Heterozygote
KW - Homocysteine/blood
KW - Homozygote
KW - Humans
KW - Kaplan-Meier Estimate
KW - Male
KW - Methylenetetrahydrofolate Reductase (NADPH2)/genetics
KW - Middle Aged
KW - Myocardial Infarction/etiology
KW - Phenotype
KW - Polymorphism, Single Nucleotide
KW - Predictive Value of Tests
KW - Proportional Hazards Models
KW - ROC Curve
KW - Risk Assessment
KW - Risk Factors
KW - Stroke/etiology
KW - Time Factors
U2 - 10.1016/j.numecd.2016.09.005
DO - 10.1016/j.numecd.2016.09.005
M3 - SCORING: Journal article
C2 - 27773468
VL - 27
SP - 168
EP - 175
JO - NUTR METAB CARDIOVAS
JF - NUTR METAB CARDIOVAS
SN - 0939-4753
IS - 2
ER -
