The TT genotype of the methylenetetrahydrofolate reductase C677T gene polymorphism is associated with the extent of coronary atherosclerosis in patients at high risk for coronary artery disease

Gardemann, Andreas; Weidemann, Hermann; Philipp, Monika; Katz, Norbert; Tillmanns, Harald; Fw, Hehrlein; Haberbosch, Werner

doi:10.1053/euhj.1998.1340

Cited by 55 publications

(21 citation statements)

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“…Moreover, Okada et al [82] have found an independent correlation between the severity of coronary atherosclerosis and Hcy levels in type 2 diabetics in contrast to nondiabetics. Finally, Gardemann et al [83] observed an association of the magnitude of coronary atherosclerosis with a thermolabile variant of N 5 ,N 10 -methylenetretrahydrofolate reductase (associated with a lower activity of the remethylation pathway and, consequently, higher Hcy levels) exclusively in those with fasting glucose level greater than 112 mg/dL (6.22 mmol/L).…”

Section: Relevance Of Elevated Hcy For Atherogenesis In the Presence mentioning

confidence: 99%

Nontraditional atherosclerotic risk factors and extent of coronary atherosclerosis in patients with combined impaired fasting glucose and impaired glucose tolerance

et al. 2007

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Section: Relevance Of Elevated Hcy For Atherogenesis In the Presence mentioning

confidence: 99%

Nontraditional atherosclerotic risk factors and extent of coronary atherosclerosis in patients with combined impaired fasting glucose and impaired glucose tolerance

et al. 2007

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“…Some data support this possibility. In the largest study of the C677T MTHFR polymorphism and CVD risk undertaken to date, which included 2453 white male subjects, Gardemann et al (66) showed that the TT homozygosity was significantly associated with a graded coronary heart disease score obtained by angiography. Notably, this relation was confined to subjects with a high coronary risk as determined by a proatherogenic lipoprotein profile or elevated glucose concentration.…”

Section: Mthfr Polymorphism Genetics and Ethnicitymentioning

confidence: 99%

The controversy over homocysteine and cardiovascular risk

Ueland

Refsum

Beresford

et al. 2000

The American Journal of Clinical Nutrition

451

235

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Elevated plasma total homocysteine (tHcy) is a risk factor for occlusive cardiovascular disease (CVD). This concept is based on the observations of premature vascular disease in patients with homocystinuria, the relation between tHcy and both clinical CVD as well as preclinical atherosclerotic disease, the relation between tHcy in children and CVD in their parents or relatives, and reduction in CVD or surrogate endpoints after tHcy-lowering intervention with B vitamins. Plausible mechanisms include the in vivo interference with nitric oxide-dependent reactive vasodilatation. Some observations have raised questions about tHcy as a risk factor. 1) Some prospective studies showed a weak relation or no relation between tHcy and CVD. 2) Several traditional risk factors are associated with tHcy and may confound the relation between tHcy and CVD. 3) tHcy is related to renal function, and hyperhomocysteinemia may reflect early nephrosclerosis. 4) The C677T transition of the methylenetetrahydrofolate reductase gene causes a moderate increase in tHcy but no or only minor increased CVD risk. However, the strength of some of these arguments can be questioned because there is increasing evidence that tHcy is a proximate risk factor provoking the acute event, it strongly interacts with traditional risk factors, and it may predict CVD or death in patients with chronic renal failure. Furthermore, the studies of the C677T polymorphism lack statistical power, and the TT genotype may even modulate CVD risk independently of homocysteine. Thus, only placebocontrolled intervention studies with tHcy-lowering B vitamins and clinical endpoints can provide additional valid arguments for the debate over whether tHcy is a causal CVD risk factor. Am J Clin Nutr 2000;72:324-32.KEY WORDS Homocysteine, cardiovascular disease, methylenetetrahydrofolate reductase polymorphism, renal, nephrosclerosis INTRODUCTIONPatients with the inborn metabolic error homocystinuria have markedly elevated homocysteine concentrations in plasma and urine and occlusive vascular disease in early adulthood or even in childhood (1). On the basis of these observations, McCully (2) formulated the homocysteine theory of atherosclerosis in 1969 (2). In 1976, Wilcken and Wilcken (3) published their pioneering work on abnormal homocysteine metabolism in patients with coronary artery disease. Since then, convincing evidence has been gathered on the relation between moderate elevation of plasma total homocysteine (tHcy) and the risk of occlusive vascular disease in the coronary, cerebral (4), and peripheral arteries and, more recently, of venous thrombosis (5-7). The literature on this subject now includes > 120 articles reporting on > 12 000 patient-control subject sets. Almost all of the retrospective case-control studies and most of the prospective studies support the concept of hyperhomocysteinemia as a risk factor for cardiovascular disease (CVD; 6, 8), and several meta-analyses showed similar, consistent results, as summarized in Figure 1.Some observations may s...

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“…Again, although we do not found a statistically significant difference in the genotypes distribution in the subset of subjects with tHcy levels higher than 15 mol/l, data argue in favour of the Jakubowski hypothesis [70]. In fact, previously studies pointed in the same direction [75][76][77]. Also, a promoter variant located at the PON1 gene has been shown to interact with the TT genotype of the C677T variant of the MTHFR gene [75,78].…”

Section: Paraoxonase Genotypes Modulates In Vivo Thcy Levels?mentioning

confidence: 55%

Concerning Arterial Hypertension, Homocysteine and Paraoxonase-1

Rodrı́guez-Esparragón¹,

Caballero-Hidalgo²,

Hernandez-Trujillo³

et al. 2007

CHYR

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An increased concentration of homocysteine (Hcy) is considered an independent and graded cardiovascular risk factor. Hcy can be non-specifically activated by methionyl-tRNA synthetase to Homocysteine thiolactone (HTL). HTL is hydrolyzed to Hcy by the paraoxonase/Thiolactonase (PON1) enzyme. PON1 is a calcium-dependent esterase synthesized in the liver and contained in plasma High-Density Lipoproteins (HDLs). The PON1 gene is polymorphic. High thiolactonase activity was associated with L55 and R192 alleles, whereas low thiolactonase activity was associated with M55 and Q192 alleles. This study provides a brief overview of some of the mechanisms by which Hcy affects vascular function and the evidence that accounts for their relevance in hypertension. The hypothesis by which alleles encoding high thiolactonase forms of PON1 might confer vascular protection under certain environmental conditions is discussed. We also evaluated these alleles and conditions in patients and controls from our institutional records.

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The TT genotype of the methylenetetrahydrofolate reductase C677T gene polymorphism is associated with the extent of coronary atherosclerosis in patients at high risk for coronary artery disease

Abstract: The present study extends previous observations by the finding that carriers of the N5,N10-methylenetetrahydrofolate reductase C677T TT genotype with various coronary high risk profiles had clearly higher coronary heart disease scores than individuals with at least one C677T C allele.

Cited by 55 publications

References 54 publications

Nontraditional atherosclerotic risk factors and extent of coronary atherosclerosis in patients with combined impaired fasting glucose and impaired glucose tolerance

Nontraditional atherosclerotic risk factors and extent of coronary atherosclerosis in patients with combined impaired fasting glucose and impaired glucose tolerance

The controversy over homocysteine and cardiovascular risk

Concerning Arterial Hypertension, Homocysteine and Paraoxonase-1

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