Family-based investigation of the C677T polymorphism of the methylenetetrahydrofolate reductase gene in ischaemic heart disease

Spence, Mark S.; McGlinchey, Paul G.; Patterson, Chris; Belton, Christine; Murphy, Gillian; McMaster, Dorothy; Fogarty, Damian; Evans, Alun; McKeown, Pascal

doi:10.1016/s0021-9150(02)00239-3

Cited by 16 publications

(16 citation statements)

References 19 publications

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“…Homozygosity for the C677T MTHFR mutation has been associated with intermediate and mild hyperhomocysteinemia (Ueland et al, 2001). C677T homozygosity is correlated with a 3-fold increased risk for premature cardiovascular disease in patients with mild hyperhomocysteinemia, even without other known risk factors, such as hypertension, hyperlipidemia, or diabetes (Yoo and Park, 2000;Mager et al, 2002;Spence et al, 2002). Patients with this mutation responded well to the folic acid treatment, which lowered the plasma homocysteine level (Ma et al, 1996;Herman et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Methylene Tetrahydrofolate Reductase C677T Mutation and Left Ventricular Hypertrophy in Turkish Patients with Type II Diabetes Mellitus

Yılmaz¹,

Ağaçhan²,

Ergen³

et al. 2004

BMB Reports

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Section: Discussionmentioning

confidence: 99%

Methylene Tetrahydrofolate Reductase C677T Mutation and Left Ventricular Hypertrophy in Turkish Patients with Type II Diabetes Mellitus

Yılmaz¹,

Ağaçhan²,

Ergen³

et al. 2004

BMB Reports

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“…54 Each variant homozygote has a decreased enzyme activity, which would result in an increased pool of methylene-THF at the expense of a decreased pool of methyl-THF. [72][73][74][75][76][77][78] A study by Rosenberg et al 79 addressed the question of whether the MTHFR 677CT alteration has an ancestral origin or has occurred repeatedly. 79 Stern and colleagues 80 investigated whether a common 677CT mutation in the MTHFR gene, which results in reduced enzyme activity in vitro, affects genomic DNA methylation.…”

Section: Methylenetetrahydrofolate Reductase (Mthfr)mentioning

confidence: 99%

Folic acid, polymorphism of methyl-group metabolism genes, and DNA methylation in relation to GI carcinogenesis

Fang

Xiao

2003

Journal of Gastroenterology

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DNA methylation is the main epigenetic modification after replication in humans. DNA (cytosine-5)-methyltransferase (DNMT) catalyzes the transfer of a methyl group from S-adenosyl-L-methionine (SAM) to C5 of cytosine within CpG dinucleotide sequences in the genomic DNA of higher eukaryotes. There is considerable evidence that aberrant DNA methylation plays an integral role in carcinogenesis. Folic acid or folate is crucial for normal DNA synthesis and can regulate DNA methylation, and through this, it affects cellular SAM levels. Folate deficiency results in DNA hypomethylation. Epidemiological studies have indicated that folic acid protects against gastrointestinal (GI) cancers. Methylene-tetrahydrofolate reductase (MTHFR) and methionine synthase (MS) are the enzymes involved in folate metabolism and are thought to influence DNA methylation. MTHFR is highly polymorphic, and the variant genotypes result in decreased MTHFR enzyme activity and lower plasma folate level. Two common MTHFR polymorphisms, 677CT (or 677TT) and A1298C, and an MS polymorphism, A-->G at 2756, have been identified. Most studies support an inverse association between folate status and the rate of colorectal adenomas and carcinomas. During human GI carcinogenesis, MTHFR is highly polymorphic, and the variant genotypes result in decreased MTHFR enzyme activity and lower plasma folate level, as well as aberrant methylation.

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“…[22][23][24][25] The effect of the thermolabile variant of the MTHFR gene on mild hyperhomocysteinemia is well established. 25 In most studies, homozygous carriers of the mutation showed increases of 2 to 3 mmol l À1 in homocysteine levels.…”

mentioning

confidence: 99%

C677T mutation of methylenetetrahydrofolate reductase gene and serum homocysteine levels in Turkish patients with coronary artery disease

Yılmaz

İşbir

Ağaçhan

et al. 2005

Cell Biochem. Funct.

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Elevated levels of homocysteine is a risk factor for coronary artery disease. The C677T transition in methylenetetrahydrofolate reductase (MTHFR) is associated with increased homocysteine levels in the general population. We analysed the association between the MTHFR C677T polymorphism and serum homocysteine concentrations in patients with coronary artery disease (CAD). Allele frequencies for the 'C' (wild-type) and 'T' alleles were 0.71 and 0.29 in CAD patients and 0.70 and 0.30 in controls, respectively. There was no difference in the distribution of MTHFR genotypes between patients with CAD and control subjects (p > 0.05). In the patient group, homocysteine levels were higher than controls but not significantly (13.99 +/- 7.44 vs. 11.77 +/- 5.18 micromol l(-1); p > 0.05). Serum homocysteine concentration was significantly higher in the TT genotype with respect to CC and CT genotypes in both the control group (p < 0.01) and patient group (p < 0.01). Systolic and diastolic blood pressures in subjects with different MTHFR genotypes did not differ significantly. In conclusion, MTHFR C677T mutation was significantly related to hyperhomocysteinemia. In spite of the clear effect of the MTHFR polymorphism on elevated homocysteine levels, we did not observe any associations among the MTHFR genotypes with a the risk of CAD in the Turkish population.

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Family-based investigation of the C677T polymorphism of the methylenetetrahydrofolate reductase gene in ischaemic heart disease

Cited by 16 publications

References 19 publications

Methylene Tetrahydrofolate Reductase C677T Mutation and Left Ventricular Hypertrophy in Turkish Patients with Type II Diabetes Mellitus

Methylene Tetrahydrofolate Reductase C677T Mutation and Left Ventricular Hypertrophy in Turkish Patients with Type II Diabetes Mellitus

Folic acid, polymorphism of methyl-group metabolism genes, and DNA methylation in relation to GI carcinogenesis

C677T mutation of methylenetetrahydrofolate reductase gene and serum homocysteine levels in Turkish patients with coronary artery disease

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