Common Mutation in Methylenetetrahydrofolate Reductase

DeLoughery, Thomas G.; Evans, Adam; Sadeghi, Abbas; McWilliams, J. E.; Henner, W. David; Taylor, Lloyd M.; Press, Richard D.

doi:10.1161/01.cir.94.12.3074

Cited by 178 publications

(48 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…12 Recent studies have investigated this mutation as a genetic risk factor for spina bifida [13][14][15] and cardiovascular disease. [16][17][18][19][20] All studies indicate that homozygotes for this transition have mildly elevated plasma homocysteine, especially in circumstances of low folate status 21,22 In this report, we describe the identification of two missense and two nonsense mutations in the MTHFR gene in four unrelated families from Turkish/Greek ancestry with severe MTHFR deficiency. Furthermore, our data contribute to the genotype/phenotype correlations in this metabolic disease.…”

Section: Introductionmentioning

confidence: 88%

Identification of four novel mutations in severe methylenetetrahydrofolate reductase deficiency

Wendel

et al. 1998

Eur J Hum Genet

View full text Add to dashboard Cite

Severe methylenetetrahydrofolate reductase (MTHFR) deficiency is an inborn error of folate metabolism, and is inherited as an autosomal recessive trait. MTHFR is a key enzyme in folate-dependent remethylation of homocysteine, and reduces 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. Patients with this severe enzymatic deficiency are biochemically characterised by homocystinuria and hypomethioninaemia, and may suffer from neurological abnormalities, mental retardation and premature vascular disease. Here we report the molecular basis of severe MTHFR deficiency in four unrelated families from Turkish/Greek ancestry. By use of reverse-transcriptase (RT)-PCR, subsequently followed by direct sequencing analysis, we were able to identify four novel mutations in the MTHFR gene: two missense (983A®G; 1027T®G) and two nonsense (1084C®T; 1711C®T) mutations. Furthermore, a splice variant containing a premature termination codon, was observed in one patient, probably as a secondary effect of the 1027T®G missense mutation. The ongoing identification and characterisation of mutations in the MTHFR gene will provide further insight into the heterogeneity of the clinical phenotype in severe MTHFR deficiency.

show abstract

Section: Introductionmentioning

confidence: 88%

Identification of four novel mutations in severe methylenetetrahydrofolate reductase deficiency

Wendel

et al. 1998

Eur J Hum Genet

View full text Add to dashboard Cite

show abstract

“…About half the general population carries at least one mutated allele and the frequency of the homozygous mutated genotype (val/val) varies from 8% to 18% depending on the population. [8][9][10][11][12][13][14][15][16][17][18][19] The MTHFR mutation was shown to render the enzyme thermolabile, and homozygotes and heterozygotes had about a 70% and 35% reduced MTHFR activity, respectively. 7 Furthermore, homozygosity for the mutation is associated with elevated levels of homocysteine in plasma.…”

Section: Introductionmentioning

confidence: 99%

Mortality risk in men is associated with a common mutation in the methylenetetrahydrofolate reductase gene (MTHFR)

Heijmans

Gussekloo

Kluft³

et al. 1999

Eur J Hum Genet

View full text Add to dashboard Cite

An elevated level of homocysteine in plasma is associated with the occurrence of cardiovascular disease. A common ala-to-val mutation in the methylenetetrahydrofolate reductase gene (MTHFR) is associated with an elevated level of plasma homocysteine. We studied the possible detrimental effects of the MTHFR mutation on mortality. Within a population-based study in the city of Leiden, the Netherlands, we first compared the MTHFR genotype distribution among 365 elderly subjects aged 85 years and over born in Leiden, and 250 young subjects aged 18 to 40 years whose families originated from the same geographical region. Second, the complete cohort of 666 subjects aged 85 years and over was followed over a period of 10 years for all-cause and cause-specific mortality and stratified according to MTHFR genotype. The frequency of the MTHFR mutation was significantly lower in the elderly than in the young (0.30 and 0.36, respectively; P = 0.03). The difference in genotype distribution was only present in men. The estimated mortality risk up to 85 years in men carrying the val/val genotype was 3.7 (95% confidence interval (CI), 1.3-10.9). Over the age of 85, mortality in men with the val/val genotype was increased 2.0-fold (95% CI, 1.1-3.9) and appeared to be attributable to cancer rather than cardiovascular causes of death. Among women aged 85 years and over, no deleterious effect of the MTHFR mutation was observed. In conclusion, the MTHFR mutation is associated with increased mortality in men in middle and old age, but not in women.

show abstract

“…A number of investigations have been done to identify whether the thermolabile mutant, MTHFR C677T causes an increased risk for cardiovascular disease. Some results suggest such a correlation (Morita et al 1997;Kang et al 1988Kang et al , 1991Gallagher et al 1996;Kluijtmans et al 1996), whereas others do not (Verhoef et al 1997;Anderson et al 1997;Ma et al 1996;Deloughery et al 1996;van Bockxmeer et al 1997;Christensen et al 1997;Wilcken et al 1996;Adams et al 1996;Brugada & Marian;1997). Arruda et al have shown that there is a correlation between homozygosity for the MTHFR C677T mutation and venous thromboembolic disease (Arruda et al 1997).…”

mentioning

confidence: 99%

Hyperhomocysteinemia and the MTHFR C677T mutation in central retinal vein occlusion

Larsson

Hultberg

Hillarp³

2000

Acta Ophthalmologica Scandinavica

View full text Add to dashboard Cite

ABSTRACT.Background: Hyperhomocysteinemia is a factor that predisposes to thrombosis, and the C677T mutation in methylene-tetrahydrofolate reductase (MTHFR) is known to give increased plasma homocysteine. We wanted to investigate if these factors were overrepresented in a group of patients with central retinal vein occlusion. Methods: 116 patients with a history of central retinal vein occlusion were examined for the presence of hyperhomocysteinemia and the MTHFR C677T mutation. Results: Compared to the control groups, there was no significant increase, neither in plasma homocysteine nor in the frequency of the MTHFR C677T mutation in the patients. Even when we looked selectively at the young patients, age less than 50 years, no difference could be detected. Conclusion: It seems that neither hyperhomocysteinemia nor the MTHFR C677T mutation is an important risk factor for the aetiology of central retinal vein occlusion.

show abstract

Common Mutation in Methylenetetrahydrofolate Reductase

Cited by 178 publications

References 13 publications

Identification of four novel mutations in severe methylenetetrahydrofolate reductase deficiency

Identification of four novel mutations in severe methylenetetrahydrofolate reductase deficiency

Mortality risk in men is associated with a common mutation in the methylenetetrahydrofolate reductase gene (MTHFR)

Hyperhomocysteinemia and the MTHFR C677T mutation in central retinal vein occlusion

Contact Info

Product

Resources

About