Homocysteine concentration in coronary artery disease: Influence of three common single nucleotide polymorphisms

被引：13

作者：

Bickel, C. ^{[1
]}

Schnabel, R. B. ^{[2
]}

Zengin, E. ^{[2
]}

Lubos, E. ^{[2
]}

Rupprecht, H. ^{[3
]}

Lackner, K. ^{[4
]}

Proust, C. ^{[5
,6
]}

Tregouet, D. ^{[5
,6
]}

Blankenberg, S. ^{[2
]}

Westermann, D. ^{[2
]}

Sinning, C. ^{[2
]}

机构：

[1] Fed Armed Forces Cent Hosp, Dept Internal Med, Koblenz, Germany

[2] Univ Heart Ctr Hamburg, Dept Gen & Intervent Cardiol, Hamburg, Germany

[3] GPR Russelsheim, Dept Med II, Russelsheim, Germany

[4] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Inst Clin Chem, Lab Med, Mainz, Germany

[5] ICAN, Paris, France

[6] UPMC Univ Paris 06, Sorbonne Univ, INSERM, UMR S 1166,Team Genom & Pathophysiol Cardiovasc, Paris, France

来源：

NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES | 2017年 / 27卷 / 02期

关键词：

Homocysteine; Coronary artery; disease; Single nucleotide; polymorphisms; Outcome; BRAIN NATRIURETIC PEPTIDE; C-REACTIVE PROTEIN; METHYLENETETRAHYDROFOLATE REDUCTASE; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; HEART-DISEASE; PLASMA HOMOCYSTEINE; FOLIC-ACID; VASCULAR-DISEASE; RISK;

D O I：

10.1016/j.numecd.2016.09.005

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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. KaplaneMeier 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: 2.9e14.6, 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. (C) 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.

引用

页码：168 / 175

页数：8

共 30 条

[11] Epigenetic modifications in cardiovascular disease [J].

Lorenzen, Johan M. ;

Martino, Filippo ;

Thum, Thomas .

BASIC RESEARCH IN CARDIOLOGY, 2012, 107 (02)

[12] Methylenetetrahydrofolate reductase polymorphism, plasma folate, homocysteine, and risk of myocardial infarction in US Physicians [J].

Ma, J ;

Stampfer, MJ ;

Hennekens, CH ;

Frosst, P ;

Selhub, J ;

Horsford, J ;

Malinow, MR ;

Willett, WC ;

Rozen, R .

CIRCULATION, 1996, 94 (10) :2410-2416

[13] Mapping genetic determinants of coronary microvascular remodeling in the spontaneously hypertensive rat [J].

Mancini, Massimiliano ;

Petretto, Enrico ;

Kleinert, Christina ;

Scavone, Angela ;

De, Tisham ;

Cook, Stuart ;

Silhavy, Jan ;

Zidek, Vaclav ;

Pravenec, Michal ;

d'Amati, Giulia ;

Camici, Paolo G. .

BASIC RESEARCH IN CARDIOLOGY, 2013, 108 (01)

[14] Hyperhomocysteinemia but not the C677T mutation of methylenetetrahydrofolate reductase is an independent risk determinant of carotid wall thickening - The Perth carotid ultrasound disease assessment study (CUDAS) [J].

McQuillan, BM ;

Beilby, JP ;

Nidorf, M ;

Thompson, PL ;

Hung, J .

CIRCULATION, 1999, 99 (18) :2383-2388

[15] The association between plasma homocysteine and coronary heart disease is modified by the MTHFR 677C>T polymorphism [J].

Mehlig, K. ;

Leander, K. ;

de Faire, U. ;

Nyberg, F. ;

Berg, C. ;

Rosengren, A. ;

Bjorck, L. ;

Zetterberg, H. ;

Blennow, K. ;

Tognon, G. ;

Toren, K. ;

Strandhagen, E. ;

Lissner, L. ;

Thelle, D. .

HEART, 2013, 99 (23) :1761-1765

[16] A SIMPLE SALTING OUT PROCEDURE FOR EXTRACTING DNA FROM HUMAN NUCLEATED CELLS [J].

MILLER, SA ;

DYKES, DD ;

POLESKY, HF .

NUCLEIC ACIDS RESEARCH, 1988, 16 (03) :1215-1215

[17]

Moat Stuart J, 2004, Hum Mutat, V23, P206, DOI 10.1002/humu.9214

[18] High-dose folic acid pretreatment blunts cardiac dysfunction during ischemia coupled to maintenance of high-energy phosphates and reduces postreperfusion injury [J].

Moens, An L. ;

Champion, Hunter C. ;

Claeys, Marc J. ;

Tavazzi, Barbara ;

Kaminski, Pawel M. ;

Wolin, Michael S. ;

Borgonjon, Dirk J. ;

Van Nassauw, Luc ;

Haile, Azeb ;

Zviman, Muz ;

Bedja, Djahida ;

Wuyts, Floris L. ;

Elsaesser, Rebecca S. ;

Cos, Paul ;

Gabrielson, Kathy L. ;

Lazzarino, Giuseppe ;

Paolocci, Nazareno ;

Timmermans, Jean-Pierre ;

Vrints, Christiaan J. ;

Kass, David A. .

CIRCULATION, 2008, 117 (14) :1810-1819

[19] Identification of mutational hot spots in LMNA encoding lamin A/C in patients with familial dilated cardiomyopathy [J].

Perrot, Andreas ;

Hussein, Shwan ;

Ruppert, Volker ;

Schmidt, Hartmut H. J. ;

Wehnert, Manfred S. ;

Duong, Nguyen Thuy ;

Posch, Maximilian G. ;

Panek, Anna ;

Dietz, Rainer ;

Kindermann, Ingrid ;

Bohm, Michael ;

Michalewska-Wludarczyk, Aleksandra ;

Richter, Anette ;

Maisch, Bernhard ;

Pankuweit, Sabine ;

Oezcelik, Cemil .

BASIC RESEARCH IN CARDIOLOGY, 2009, 104 (01) :90-99

[20] Homocysteine and methylenetetrahydrofolate reductase genotype:: association with risk of coronary heart disease and relation to inflammatory, hemostatic, and lipid parameters [J].

Rothenbacher, D ;

Fischer, HG ;

Hoffmeister, A ;

Hoffmann, MM ;

März, W ;

Bode, G ;

Rosenthal, J ;

Koenig, W ;

Brenner, H .

ATHEROSCLEROSIS, 2002, 162 (01) :193-200

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