HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit an electronic Letter to the Editor about this paper Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (59) Citing Articles via Google Scholar Google Scholar Articles by Hanson, N. Q. Articles by Tsai, M. Y. Search for Related Content PubMed PubMed Citation Articles by Hanson, N. Q. Articles by Tsai, M. Y. Related Collections Molecular Diagnostics and Genetics Lipids, Lipoproteins, and Cardiovascular Risk Factors

C677T and A1298C Polymorphisms of the Methylenetetrahydrofolate Reductase Gene: Incidence and Effect of Combined Genotypes on Plasma Fasting and Post-Methionine Load Homocysteine in Vascular Disease

¹ Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN 55455-0392.
^a Address correspondence to this author at: 420 Delaware St. SE, Mayo Mail Code 609, Minneapolis, MN 55455-0392. Fax 612-625-5622; e-mail tsaix001{at}tc.umn.edu.

Background: Moderately increased plasma concentrations of total homocysteine (tHcy) have been shown to be an important risk factor for vascular diseases. Two common polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene, the thermolabile C677T and a more recently reported A1298C polymorphism, may contribute to hyperhomocysteinemia.

Methods: Using PCR and restriction fragment length polymorphism analysis, we studied the prevalence of the C677T and A1298C MTHFR genotypes and the combined effect of these polymorphisms on plasma tHcy concentrations, as measured by HPLC with fluorometric detection, both fasting and post-methionine load (PML), in 1238 individuals.

Results: The prevalences of the C677T and A1298C genotypes did not differ significantly in 772 individuals with documented coronary artery disease (CAD), 137 individuals with deep-vein thrombosis (DVT), and 329 individuals without documented vascular disease. Individuals homozygous for the 677T allele had significantly increased fasting tHcy, particularly in the presence of low folate, compared with individuals homozygous for the wild-type allele. Neither the 1298AC nor the 1298CC genotype was associated with significantly increased fasting or PML tHcy concentrations irrespective of serum folate. Of the nine combined MTHFR genotypes, six were present in >10% of the population. Of these, the difference in mean fasting tHcy reached statistical significance (P <0.005) only in individuals with the 677TT/1298AA genotype compared with individuals with the wild-type 677CC/1298AA genotype. Differences in mean fasting tHcy did not reach statistical significance in individuals heterozygous for both MTHFR variants. We detected two 677CT/1298CC and three 677TT/1298AC individuals; only one, an 677TT/1298AC individual, had increased tHcy (both fasting and PML). No individuals had the 677TT/1298CC genotype.

Conclusions: The prevalences of the C677T and A1298C polymorphisms did not differ among individuals with CAD, DVT, or those without documented vascular disease. In contrast to the C677T polymorphism, the A1298C polymorphism is not associated with increased fasting tHcy. Although the two polymorphisms usually exist in trans configuration, crossover may occur rarely to form recombinant chromosomes.

The following articles in journals at HighWire Press have cited this article:

				S. Dayal and S. R. Lentz Murine Models of Hyperhomocysteinemia and Their Vascular Phenotypes Arterioscler. Thromb. Vasc. Biol., September 1, 2008; 28(9): 1596 - 1605. [Abstract] [Full Text] [PDF]

				R. P. Agarwal, S. M. Peters, M. Shemirani, and N. von Ahsen Improved Real-Time Multiplex Polymerase Chain Reaction Detection of Methylenetetrahydrofolate Reductase (MTHFR) 677C>T and 1298A>C Polymorphisms Using Nearest Neighbor Model-Based Probe Design J. Mol. Diagn., July 1, 2007; 9(3): 345 - 350. [Abstract] [Full Text] [PDF]

				C. McCarthy, F. Ryan, and J. Vaughan Increased Frequency of the MTHFR A1298C Mutation in an Irish Population Clin. Chem., December 1, 2004; 50(12): 2462 - 2463. [Full Text] [PDF]

				A. M. Devlin, E. Arning, T. Bottiglieri, F. M. Faraci, R. Rozen, and S. R. Lentz Effect of Mthfr genotype on diet-induced hyperhomocysteinemia and vascular function in mice Blood, April 1, 2004; 103(7): 2624 - 2629. [Abstract] [Full Text] [PDF]

				H. Refsum, A. D. Smith, P. M. Ueland, E. Nexo, R. Clarke, J. McPartlin, C. Johnston, F. Engbaek, J. Schneede, C. McPartlin, et al. Facts and Recommendations about Total Homocysteine Determinations: An Expert Opinion Clin. Chem., January 1, 2004; 50(1): 3 - 32. [Abstract] [Full Text] [PDF]

				R. Castro, I. Rivera, P. Ravasco, C. Jakobs, H.J. Blom, M.E. Camilo, and I.T. de Almeida 5,10-Methylenetetrahydrofolate reductase 677C->T and 1298A->C mutations are genetic determinants of elevated homocysteine QJM, April 1, 2003; 96(4): 297 - 303. [Abstract] [Full Text] [PDF]

				K. Robien and C. M. Ulrich 5,10-Methylenetetrahydrofolate Reductase Polymorphisms and Leukemia Risk: A HuGE Minireview Am. J. Epidemiol., April 1, 2003; 157(7): 571 - 582. [Abstract] [Full Text] [PDF]

				T. Suormala, G. Gamse, and B. Fowler 5,10-Methylenetetrahydrofolate Reductase (MTHFR) Assay in the Forward Direction: Residual Activity in MTHFR Deficiency Clin. Chem., June 1, 2002; 48(6): 835 - 843. [Abstract] [Full Text] [PDF]