(Circulation. 1996;93:7-9.)
© 1996 American Heart Association, Inc.
Articles |
Relation Between Folate Status, a Common Mutation in Methylenetetrahydrofolate Reductase, and Plasma Homocysteine Concentrations
From the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Mass (P.F.J., A.G.B., I.H.R., J.S.); the NHLBI Family Heart Study, University of Utah Cardiovascular Genetics Research Clinic, Salt Lake City (R.R.W.); the NHLBI Family Heart Study, Framingham, Mass, and Boston (Mass) University School of Medicine (R.C.E.); the NHLBI Family Heart Study Central Laboratory, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis (J.H.E.); and the Departments of Human Genetics, Pediatrics, and Biology, McGill University, Montreal (Quebec) Children's Hospital (R.R.).
Correspondence to Rima Rozen, Montreal Children's Hospital, 2300 Tupper St, Montreal, Quebec, Canada H3H 1P3.
Background Methylenetetrahydrofolate reductase (MTHFR) synthesizes 5-methyltetrahydrofolate, the major carbon donor in remethylation of homocysteine to methionine. A common MTHFR mutation, an alanine-to-valine substitution, renders the enzyme thermolabile and may cause elevated plasma levels of the amino acid homocysteine.
Methods and Results To assess the potential interaction
between this mutation and vitamin coenzymes in homocysteine
metabolism, we screened 365 individuals from the NHLBI
Family Heart Study. Among individuals with lower plasma folate
concentrations (<15.4 nmol/L), those with the homozygous mutant
genotype had total fasting homocysteine levels that were 24%
greater (P<.05) than individuals with the normal
genotype. A difference between genotypes was not seen
among individuals with folate levels 
15.4 nmol/L.
Conclusions Individuals with thermolabile MTHFR may have a higher folate requirement for regulation of plasma homocysteine concentrations; folate supplementation may be necessary to prevent fasting hyperhomocysteinemia in such persons.
Key Words: enzymes • homocysteine • amino acids • metabolism • genetics
This article has been cited by other articles:
 |
|
 |
|
  S. Afzal, S. A. Jensen, B. Vainer, U. Vogel, J. P. Matsen, J. B. Sorensen, P. K. Andersen, and H. E. Poulsen MTHFR polymorphisms and 5-FU-based adjuvant chemotherapy in colorectal cancer Ann. Onc., May 22, 2009; (2009) mdp046v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Caudill, N. Dellschaft, C. Solis, S. Hinkis, A. A. Ivanov, S. Nash-Barboza, K. E. Randall, B. Jackson, G. N. Solomita, and F. Vermeylen Choline Intake, Plasma Riboflavin, and the Phosphatidylethanolamine N-Methyltransferase G5465A Genotype Predict Plasma Homocysteine in Folate-Deplete Mexican-American Men with the Methylenetetrahydrofolate Reductase 677TT Genotype J. Nutr., April 1, 2009; 139(4): 727 - 733. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. de Jonge, W. J. E. Tissing, J. H. Hooijberg, G. Jansen, G. J. L. Kaspers, J. Lindemans, G. J. Peters, and R. Pieters Polymorphisms in folate-related genes and risk of pediatric acute lymphoblastic leukemia Blood, March 5, 2009; 113(10): 2284 - 2289. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. FISHER and B. N. CRONSTEIN Metaanalysis of Methylenetetrahydrofolate Reductase (MTHFR) Polymorphisms Affecting Methotrexate Toxicity J Rheumatol, March 1, 2009; 36(3): 539 - 545. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Schatzkin, C. C. Abnet, A. J. Cross, M. Gunter, R. Pfeiffer, M. Gail, U. Lim, and G. Davey-Smith Mendelian Randomization: How It Can--and Cannot--Help Confirm Causal Relations between Nutrition and Cancer Cancer Prevention Research, February 1, 2009; 2(2): 104 - 113. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Ganji and M. R. Kafai Demographic, Lifestyle, and Health Characteristics and Serum B Vitamin Status Are Determinants of Plasma Total Homocysteine Concentration in the Post-Folic Acid Fortification Period, 1999-2004 J. Nutr., February 1, 2009; 139(2): 345 - 352. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Y. Tsai, C. M. Loria, J. Cao, Y. Kim, D. Siscovick, P. J. Schreiner, and N. Q. Hanson Clinical Utility of Genotyping the 677C>T Variant of Methylenetetrahydrofolate Reductase in Humans Is Decreased in the Post-Folic Acid Fortification Era J. Nutr., January 1, 2009; 139(1): 33 - 37. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Siekmeier, T. Grammer, and W. Marz Roles of Oxidants, Nitric Oxide, and Asymmetric Dimethylarginine in Endothelial Function Journal of Cardiovascular Pharmacology and Therapeutics, December 1, 2008; 13(4): 279 - 297. [Abstract] [PDF]
|
|
|
|
 |
|
 Q.-H. Yang, L. D Botto, M. Gallagher, J. Friedman, C. L Sanders, D. Koontz, S. Nikolova, J D. Erickson, and K. Steinberg Prevalence and effects of gene-gene and gene-nutrient interactions on serum folate and serum total homocysteine concentrations in the United States: findings from the third National Health and Nutrition Examination Survey DNA Bank Am. J. Clinical Nutrition, July 1, 2008; 88(1): 232 - 246. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Ulrich, M. Neuhouser, A. Y. Liu, A. Boynton, J. F. Gregory III, B. Shane, S. J. James, M. C. Reed, and H. F. Nijhout Mathematical Modeling of Folate Metabolism: Predicted Effects of Genetic Polymorphisms on Mechanisms and Biomarkers Relevant to Carcinogenesis Cancer Epidemiol. Biomarkers Prev., July 1, 2008; 17(7): 1822 - 1831. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Wagner and M. J Koury S-Adenosylhomocysteine a better indicator of vascular disease than homocysteine? Am. J. Clinical Nutrition, December 1, 2007; 86(6): 1581 - 1585. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I.M. van Beynum, M. den Heijer, H.J. Blom, and L. Kapusta The MTHFR 677C->T polymorphism and the risk of congenital heart defects: a literature review and meta-analysis QJM, December 1, 2007; 100(12): 743 - 753. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Siva, M. De Lange, D. Clayton, S. Monteith, T. Spector, and M.J. Brown The heritability of plasma homocysteine, and the influence of genetic variation in the homocysteine methylation pathway QJM, August 1, 2007; 100(8): 495 - 499. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Zittan, M. Preis, I. Asmir, A. Cassel, N. Lindenfeld, S. Alroy, D. A. Halon, B. S. Lewis, A. Shiran, J. E. Schliamser, et al. High frequency of vitamin B12 deficiency in asymptomatic individuals homozygous to MTHFR C677T mutation is associated with endothelial dysfunction and homocysteinemia Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H860 - H865. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Forges, P. Monnier-Barbarino, J.M. Alberto, R.M. Gueant-Rodriguez, J.L. Daval, and J.L. Gueant Impact of folate and homocysteine metabolism on human reproductive health Hum. Reprod. Update, May 1, 2007; 13(3): 225 - 238. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. I. Holm, S. Hustad, P. M. Ueland, S. E. Vollset, T. Grotmol, and J. Schneede Modulation of the Homocysteine-Betaine Relationship by Methylenetetrahydrofolate Reductase 677 C->T Genotypes and B-Vitamin Status in a Large-Scale Epidemiological Study J. Clin. Endocrinol. Metab., April 1, 2007; 92(4): 1535 - 1541. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. D. Bezemer, C. J. M. Doggen, H. L. Vos, and F. R. Rosendaal No Association Between the Common MTHFR 677C->T Polymorphism and Venous Thrombosis: Results From the MEGA Study Arch Intern Med, March 12, 2007; 167(5): 497 - 501. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Lewis, R. M. Harbord, R. Harris, and G. D. Smith Meta-analyses of Observational and Genetic Association Studies of Folate Intakes or Levels and Breast Cancer Risk. J Natl Cancer Inst, November 15, 2006; 98(22): 1607 - 1622. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Ganji and M. R Kafai Population reference values for plasma total homocysteine concentrations in US adults after the fortification of cereals with folic acid. Am. J. Clinical Nutrition, November 1, 2006; 84(5): 989 - 994. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. L. Webb, M. F. Rudd, G. S. Sellick, R. El Galta, L. Bethke, W. Wood, O. Fletcher, S. Penegar, L. Withey, M. Qureshi, et al. Search for low penetrance alleles for colorectal cancer through a scan of 1467 non-synonymous SNPs in 2575 cases and 2707 controls with validation by kin-cohort analysis of 14 704 first-degree relatives Hum. Mol. Genet., November 1, 2006; 15(21): 3263 - 3271. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Sharp, Z. Miedzybrodzka, A. H. Cardy, J. Inglis, L. Madrigal, S. Barker, D. Chesney, C. Clark, and N. Maffulli The C677T Polymorphism in the Methylenetetrahydrofolate Reductase Gene (MTHFR), Maternal Use of Folic Acid Supplements, and Risk of Isolated Clubfoot: A Case-Parent-Triad Analysis Am. J. Epidemiol., November 1, 2006; 164(9): 852 - 861. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. C. Dinleyici, B. Kirel, O. Alatas, H. Muslumanoglu, Z. Kilic, and N. Dogruel Plasma Total Homocysteine Levels in Children with Type 1 Diabetes: Relationship with Vitamin Status, Methylene Tetrahydrofolate Reductase Genotype, Disease Parameters and Coronary Risk Factors J Trop Pediatr, August 1, 2006; 52(4): 260 - 266. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. L. N Husemoen, U. Toft, M. Fenger, T. Jorgensen, N. Johansen, and A. Linneberg The association between atopy and factors influencing folate metabolism: is low folate status causally related to the development of atopy? Int. J. Epidemiol., August 1, 2006; 35(4): 954 - 961. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. J. Kullo, K. Ding, E. Boerwinkle, S. T. Turner, T. H. Mosley Jr, S. L.R. Kardia, and M. de Andrade Novel Genomic Loci Influencing Plasma Homocysteine Levels Stroke, July 1, 2006; 37(7): 1703 - 1709. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Niclot, Q. Pruvot, C. Besson, D. Savoy, E. Macintyre, G. Salles, N. Brousse, B. Varet, P. Landais, P. Taupin, et al. Implication of the folate-methionine metabolism pathways in susceptibility to follicular lymphomas Blood, July 1, 2006; 108(1): 278 - 285. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Tamura and M. F. Picciano Folate and human reproduction Am. J. Clinical Nutrition, May 1, 2006; 83(5): 993 - 1016. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A Houghton, K. L Sherwood, R. Pawlosky, S. Ito, and D. L O'Connor [6S]-5-Methyltetrahydrofolate is at least as effective as folic acid in preventing a decline in blood folate concentrations during lactation. Am. J. Clinical Nutrition, April 1, 2006; 83(4): 842 - 850. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M Devlin, R. Clarke, J. Birks, J. G. Evans, and C. H Halsted Interactions among polymorphisms in folate-metabolizing genes and serum total homocysteine concentrations in a healthy elderly population Am. J. Clinical Nutrition, March 1, 2006; 83(3): 708 - 713. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N Mtiraoui, W Zammiti, L Ghazouani, N J. Braham, S Saidi, R R Finan, W Y Almawi, and T Mahjoub Methylenetetrahydrofolate reductase C677T and A1298C polymorphism and changes in homocysteine concentrations in women with idiopathic recurrent pregnancy losses Reproduction, February 1, 2006; 131(2): 395 - 401. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. McNulty, L. R. C. Dowey, J.J. Strain, A. Dunne, M. Ward, A. M. Molloy, L. B. McAnena, J. P. Hughes, M. Hannon-Fletcher, and J. M. Scott Riboflavin Lowers Homocysteine in Individuals Homozygous for the MTHFR 677C->T Polymorphism Circulation, January 3, 2006; 113(1): 74 - 80. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. V. Podgoreanu and D. A. Schwinn New Paradigms in Cardiovascular Medicine: Emerging Technologies and Practices: Perioperative Genomics J. Am. Coll. Cardiol., December 6, 2005; 46(11): 1965 - 1977. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. J. Powers Interaction among Folate, Riboflavin, Genotype, and Cancer, with Reference to Colorectal and Cervical Cancer J. Nutr., December 1, 2005; 135(12): 2960S - 2966S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-K. Kuo, F. A. Sorond, J.-H. Chen, A. Hashmi, W. P. Milberg, and L. A. Lipsitz The Role of Homocysteine in Multisystem Age-Related Problems: A Systematic Review J. Gerontol. A Biol. Sci. Med. Sci., September 1, 2005; 60(9): 1190 - 1201. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Yamada, J. R. Strahler, P. C. Andrews, and R. G. Matthews Regulation of human methylenetetrahydrofolate reductase by phosphorylation PNAS, July 26, 2005; 102(30): 10454 - 10459. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E Chiuve, E. L Giovannucci, S. E Hankinson, D. J Hunter, M. J Stampfer, W. C Willett, and E. B Rimm Alcohol intake and methylenetetrahydrofolate reductase polymorphism modify the relation of folate intake to plasma homocysteine Am. J. Clinical Nutrition, July 1, 2005; 82(1): 155 - 162. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Li, L. Pickell, Y. Liu, Q. Wu, J. S Cohn, and R. Rozen Maternal methylenetetrahydrofolate reductase deficiency and low dietary folate lead to adverse reproductive outcomes and congenital heart defects in mice Am. J. Clinical Nutrition, July 1, 2005; 82(1): 188 - 195. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O Buchel, T Roskams, B Van Damme, F Nevens, J Pirenne, and J Fevery Nodular regenerative hyperplasia, portal vein thrombosis, and avascular hip necrosis due to hyperhomocysteinaemia Gut, July 1, 2005; 54(7): 1021 - 1023. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M von Castel-Dunwoody, G. P. Kauwell, K. P Shelnutt, J. D Vaughn, E. R Griffin, D. R Maneval, D. W Theriaque, and L. B Bailey Transcobalamin 776C->G polymorphism negatively affects vitamin B-12 metabolism Am. J. Clinical Nutrition, June 1, 2005; 81(6): 1436 - 1441. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. R. Davis, E. P. Quinlivan, K. P. Shelnutt, D. R. Maneval, H. Ghandour, A. Capdevila, B. S. Coats, C. Wagner, J. Selhub, L. B. Bailey, et al. The Methylenetetrahydrofolate Reductase 677C->T Polymorphism and Dietary Folate Restriction Affect Plasma One-Carbon Metabolites and Red Blood Cell Folate Concentrations and Distribution in Women J. Nutr., May 1, 2005; 135(5): 1040 - 1044. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. R. Davis, E. P. Quinlivan, K. P. Shelnutt, H. Ghandour, A. Capdevila, B. S. Coats, C. Wagner, B. Shane, J. Selhub, L. B. Bailey, et al. Homocysteine Synthesis Is Elevated but Total Remethylation Is Unchanged by the Methylenetetrahydrofolate Reductase 677C->T Polymorphism and by Dietary Folate Restriction in Young Women J. Nutr., May 1, 2005; 135(5): 1045 - 1050. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Beck and B. Berman Review of Thrombophilic States Clinical Pediatrics, April 1, 2005; 44(3): 193 - 199. [PDF]
|
|
|
|
|
|
C. Papoutsakis, N. Yiannakouris, Y. Manios, E. Papaconstantinou, F. Magkos, K. H. Schulpis, A. Zampelas, and A. L. Matalas Plasma Homocysteine Concentrations in Greek Children Are Influenced by an Interaction between the Methylenetetrahydrofolate Reductase C677T Genotype and Folate Status J. Nutr., March 1, 2005; 135(3): 383 - 388. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. L.J. Kelly, O. R. Neaga, B. C. Schwahn, R. Rozen, and J. M. Trasler Infertility in 5,10-Methylenetetrahydrofolate Reductase (MTHFR)-Deficient Male Mice Is Partially Alleviated by Lifetime Dietary Betaine Supplementation Biol Reprod, March 1, 2005; 72(3): 667 - 677. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S Najib and V Sanchez-Margalet Homocysteine thiolactone inhibits insulin-stimulated DNA and protein synthesis: possible role of mitogen-activated protein kinase (MAPK), glycogen synthase kinase-3 (GSK-3) and p70 S6K phosphorylation J. Mol. Endocrinol., February 1, 2005; 34(1): 119 - 126. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. P. A. Kauwell Emerging Concepts in Nutrigenomics: A Preview of What Is to Come Nutr Clin Pract, February 1, 2005; 20(1): 75 - 87. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. J. Kullo and C. M. Ballantyne Conditional Risk Factors for Atherosclerosis Mayo Clin. Proc., February 1, 2005; 80(2): 219 - 230. [Abstract] [PDF]
|
|
|
|
 |
|
 W. C. Winkelmayer, R. Kramar, G. C. Curhan, A. Chandraker, G. Endler, M. Fodinger, W. H. Horl, and G. Sunder-Plassmann Fasting Plasma Total Homocysteine Levels and Mortality and Allograft Loss in Kidney Transplant Recipients: A Prospective Study J. Am. Soc. Nephrol., January 1, 2005; 16(1): 255 - 260. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Smolkova, M. Dusinska, K. Raslova, M. Barancokova, A. Kazimirova, A. Horska, V. Spustova, and A. Collins Folate levels determine effect of antioxidant supplementation on micronuclei in subjects with cardiovascular risk Mutagenesis, November 1, 2004; 19(6): 469 - 476. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Vaughn, L. B. Bailey, K. P. Shelnutt, K. M. v.-C. Dunwoody, D. R. Maneval, S. R. Davis, E. P. Quinlivan, J. F. Gregory III, D. W. Theriaque, and G. P. A. Kauwell Methionine Synthase Reductase 66A->G Polymorphism Is Associated with Increased Plasma Homocysteine Concentration When Combined with the Homozygous Methylenetetrahydrofolate Reductase 677C->T Variant J. Nutr., November 1, 2004; 134(11): 2985 - 2990. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. V Dedoussis, D. B Panagiotakos, C. Chrysohoou, C. Pitsavos, A. Zampelas, D. Choumerianou, and C. Stefanadis Effect of interaction between adherence to a Mediterranean diet and the methylenetetrahydrofolate reductase 677C->T mutation on homocysteine concentrations in healthy adults: the ATTICA Study Am. J. Clinical Nutrition, October 1, 2004; 80(4): 849 - 854. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Refsum, A. W. Grindflek, P. M. Ueland, A. Fredriksen, K. Meyer, A. Ulvik, A. B. Guttormsen, O. E. Iversen, J. Schneede, and B. F. Kase Screening for Serum Total Homocysteine in Newborn Children Clin. Chem., October 1, 2004; 50(10): 1769 - 1784. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Craig Betaine in human nutrition Am. J. Clinical Nutrition, September 1, 2004; 80(3): 539 - 549. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Narayanan, J. McConnell, J. Little, L. Sharp, C. J. Piyathilake, H. Powers, G. Basten, and S. J. Duthie Associations between Two Common Variants C677T and A1298C in the Methylenetetrahydrofolate Reductase Gene and Measures of Folate Metabolism and DNA Stability (Strand Breaks, Misincorporated Uracil, and DNA Methylation Status) in Human Lymphocytes In vivo Cancer Epidemiol. Biomarkers Prev., September 1, 2004; 13(9): 1436 - 1443. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. A. Manolio, E. Boerwinkle, C. J. O'Donnell, and A. F. Wilson Genetics of Ultrasonographic Carotid Atherosclerosis Arterioscler. Thromb. Vasc. Biol., September 1, 2004; 24(9): 1567 - 1577. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Chen, S. M. Zhang, M. A. Schwarzschild, M. A. Hernan, G. Logroscino, W. C. Willett, and A. Ascherio Folate Intake and Risk of Parkinson's Disease Am. J. Epidemiol., August 15, 2004; 160(4): 368 - 375. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Terzolo, B. Allasino, S. Bosio, E. Brusa, F. Daffara, M. Ventura, E. Aroasio, G. Sacchetto, G. Reimondo, A. Angeli, et al. Hyperhomocysteinemia in Patients with Cushing's Syndrome J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 3745 - 3751. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Cantu, E. Alonso, A. Jara, L. Martinez, C. Rios, M. d. l. A. Fernandez, I. Garcia, and F. Barinagarrementeria Hyperhomocysteinemia, Low Folate and Vitamin B12 Concentrations, and Methylene Tetrahydrofolate Reductase Mutation in Cerebral Venous Thrombosis Stroke, August 1, 2004; 35(8): 1790 - 1794. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. R. McLean, P. F. Jacques, J. Selhub, K. L. Tucker, E. J. Samelson, K. E. Broe, M. T. Hannan, L. A. Cupples, and D. P. Kiel Homocysteine as a Predictive Factor for Hip Fracture in Older Persons N. Engl. J. Med., May 13, 2004; 350(20): 2042 - 2049. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Chrysohoou, D. B Panagiotakos, C. Pitsavos, A. Zeimbekis, A. Zampelas, L. Papademetriou, C. Masoura, and C. Stefanadis The associations between smoking, physical activity, dietary habits and plasma homocysteine levels in cardiovascular disease-free people: the 'ATTICA' study Vascular Medicine, May 1, 2004; 9(2): 117 - 123. [Abstract] [PDF]
|
|
|
|
|
|
M. E. Martinez, S. M Henning, and D. S Alberts Folate and colorectal neoplasia: relation between plasma and dietary markers of folate and adenoma recurrence Am. J. Clinical Nutrition, April 1, 2004; 79(4): 691 - 697. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Townsend, S. R. Davis, A. D. Mackey, and J. F. Gregory III Folate deprivation reduces homocysteine remethylation in a human intestinal epithelial cell culture model: role of serine in one-carbon donation Am J Physiol Gastrointest Liver Physiol, April 1, 2004; 286(4): G588 - G595. [Abstract] [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]
|
|
|
|
|
|
L. Sharp and J. Little Polymorphisms in Genes Involved in Folate Metabolism and Colorectal Neoplasia: A HuGE Review Am. J. Epidemiol., March 1, 2004; 159(5): 423 - 443. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Shrubsole, Y.-T. Gao, Q. Cai, X. O. Shu, Q. Dai, J. R. Hebert, F. Jin, and W. Zheng MTHFR Polymorphisms, Dietary Folate Intake, and Breast Cancer Risk: Results from the Shanghai Breast Cancer Study Cancer Epidemiol. Biomarkers Prev., February 1, 2004; 13(2): 190 - 196. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Palomba, T. Russo, F. Orio Jr, A. Sammartino, F. M. Sbano, C. Nappi, A. Colao, P. Mastrantonio, G. Lombardi, and F. Zullo Lipid, glucose and homocysteine metabolism in women treated with a GnRH agonist with or without raloxifene Hum. Reprod., February 1, 2004; 19(2): 415 - 421. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Voetsch and J. Loscalzo Genetic Determinants of Arterial Thrombosis Arterioscler. Thromb. Vasc. Biol., February 1, 2004; 24(2): 216 - 229. [Abstract] [Full Text]
|
|
|
|
 |
|
 S. R. Davis, P. W. Stacpoole, J. Williamson, L. S. Kick, E. P. Quinlivan, B. S. Coats, B. Shane, L. B. Bailey, and J. F. Gregory III Tracer-derived total and folate-dependent homocysteine remethylation and synthesis rates in humans indicate that serine is the main one-carbon donor Am J Physiol Endocrinol Metab, February 1, 2004; 286(2): E272 - E279. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-J. Sohn, R. Croxford, Z. Yates, M. Lucock, and Y.-I. Kim Effect of the Methylenetetrahydrofolate Reductase C677T Polymorphism on Chemosensitivity of Colon and Breast Cancer Cells to 5-Fluorouracil and Methotrexate J Natl Cancer Inst, January 21, 2004; 96(2): 134 - 144. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R Amorim, E. E Castilla, and I. M Orioli Is there a familial link between Down's syndrome and neural tube defects? Population and familial survey BMJ, January 10, 2004; 328(7431): 84. [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]
|
|
|
|
 |
|
 G C Icke, M Dennis, S Sjollema, D J Nicol, and J W Eikelboom Red cell N5-methyltetrahydrofolate concentrations and C677T methylenetetrahydrofolate reductase genotype in patients with stroke J. Clin. Pathol., January 1, 2004; 57(1): 54 - 57. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Hassan, B. J. Hunt, M. O'Sullivan, R. Bell, R. D'Souza, S. Jeffery, J. M. Bamford, and H. S. Markus Homocysteine is a risk factor for cerebral small vessel disease, acting via endothelial dysfunction Brain, January 1, 2004; 127(1): 212 - 219. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Krajinovic, S. Lamothe, D. Labuda, E. Lemieux-Blanchard, Y. Theoret, A. Moghrabi, and D. Sinnett Role of MTHFR genetic polymorphisms in the susceptibility to childhood acute lymphoblastic leukemia Blood, January 1, 2004; 103(1): 252 - 257. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Koch, G. Ndrepepa, J. Mehilli, S. Braun, M. Burghartz, H. Lengnick, K. Kolling, A. Schomig, and A. Kastrati Homocysteine Status and Polymorphisms of Methylenetetrahydrofolate Reductase Are Not Associated With Restenosis After Stenting in Coronary Arteries Arterioscler. Thromb. Vasc. Biol., December 1, 2003; 23(12): 2229 - 2234. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. D. Spotila, P. F. Jacques, P. B. Berger, K. V. Ballman, R. C. Ellison, and R. Rozen Age Dependence of the Influence of Methylenetetrahydrofolate Reductase Genotype on Plasma Homocysteine Level Am. J. Epidemiol., November 1, 2003; 158(9): 871 - 877. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. T. Russo, S. Friso, P. F. Jacques, G. Rogers, D. Cucinotta, P. W. F. Wilson, J. M. Ordovas, I. H. Rosenberg, and J. Selhub Age and Gender Affect the Relation between Methylenetetrahydrofolate Reductase C677T Genotype and Fasting Plasma Homocysteine Concentrations in the Framingham Offspring Study Cohort J. Nutr., November 1, 2003; 133(11): 3416 - 3421. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. B. Bailey Folate, Methyl-Related Nutrients, Alcohol, and the MTHFR 677C->T Polymorphism Affect Cancer Risk: Intake Recommendations J. Nutr., November 1, 2003; 133(11): 3748S - 3753. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. M. Shaw, H. Zhu, E. J. Lammer, W. Yang, and R. H. Finnell Genetic Variation of Infant Reduced Folate Carrier (A80G) and Risk of Orofacial and Conotruncal Heart Defects Am. J. Epidemiol., October 15, 2003; 158(8): 747 - 752. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Zetterberg, A. Zafiropoulos, D. A. Spandidos, L. Rymo, and K. Blennow Gene-gene interaction between fetal MTHFR 677C>T and transcobalamin 776C>G polymorphisms in human spontaneous abortion Hum. Reprod., September 1, 2003; 18(9): 1948 - 1950. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Lathrop Stern, B. Shane, P. J. Bagley, M. Nadeau, V. Shih, and J. Selhub Combined Marginal Folate and Riboflavin Status Affect Homocysteine Methylation in Cultured Immortalized Lymphocytes from Persons Homozygous for the MTHFR C677T Mutation J. Nutr., September 1, 2003; 133(9): 2716 - 2720. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Li, L. Sun, H. Zhang, Y. Liao, D. Wang, B. Zhao, Z. Zhu, J. Zhao, A. Ma, Y. Han, et al. Elevated Plasma Homocysteine Was Associated With Hemorrhagic and Ischemic Stroke, but Methylenetetrahydrofolate Reductase Gene C677T Polymorphism Was a Risk Factor for Thrombotic Stroke: A Multicenter Case-Control Study in China Stroke, September 1, 2003; 34(9): 2085 - 2090. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. M. Martinez-Taboada, M. J. Bartolome, M. D. Fernandez-Gonzalez, R. Blanco, V. Rodriguez-Valverde, and M. Lopez-Hoyos Homocysteine levels in polymyalgia rheumatica and giant cell arteritis: influence of corticosteroid therapy Rheumatology, September 1, 2003; 42(9): 1055 - 1061. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kishi, J. Griener, C. Cheng, S. Das, E. H. Cook, D. Pei, M. Hudson, J. Rubnitz, J. T. Sandlund, C.-H. Pui, et al. Homocysteine, Pharmacogenetics, and Neurotoxicity in Children With Leukemia J. Clin. Oncol., August 15, 2003; 21(16): 3084 - 3091. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Inamoto, T. Katsuya, Y. Kokubo, T. Mannami, T. Asai, S. Baba, J. Ogata, H. Tomoike, and T. Ogihara Association of Methylenetetrahydrofolate Reductase Gene Polymorphism With Carotid Atherosclerosis Depending on Smoking Status in a Japanese General Population Stroke, July 1, 2003; 34(7): 1628 - 1633. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. S. Brown, L. A.J. Kluijtmans, I. S. Young, J. Woodside, J. W.G. Yarnell, D. McMaster, L. Murray, A. E. Evans, C. A. Boreham, H. McNulty, et al. Genetic Evidence That Nitric Oxide Modulates Homocysteine: The NOS3 894TT Genotype Is a Risk Factor for Hyperhomocystenemia Arterioscler. Thromb. Vasc. Biol., June 1, 2003; 23(6): 1014 - 1020. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Cohen, V. Panet-Raymond, N. Sabbaghian, I. Morin, G. Batist, and R. Rozen Methylenetetrahydrofolate Reductase Polymorphism in Advanced Colorectal Cancer: A Novel Genomic Predictor of Clinical Response to Fluoropyrimidine-based Chemotherapy Clin. Cancer Res., May 1, 2003; 9(5): 1611 - 1615. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Guinotte, M. G. Burns, J. A. Axume, H. Hata, T. F. Urrutia, A. Alamilla, D. McCabe, A. Singgih, E. A. Cogger, and M. A. Caudill Methylenetetrahydrofolate Reductase 677C->T Variant Modulates Folate Status Response to Controlled Folate Intakes in Young Women J. Nutr., May 1, 2003; 133(5): 1272 - 1280. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Girelli, N. Martinelli, F. Pizzolo, S. Friso, O. Olivieri, C. Stranieri, E. Trabetti, G. Faccini, E. Tinazzi, P. F. Pignatti, et al. The Interaction between MTHFR 677 C->T Genotype and Folate Status Is a Determinant of Coronary Atherosclerosis Risk J. Nutr., May 1, 2003; 133(5): 1281 - 1285. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Ganji and M. R Kafai Demographic, health, lifestyle, and blood vitamin determinants of serum total homocysteine concentrations in the third National Health and Nutrition Examination Survey, 1988-1994 Am. J. Clinical Nutrition, April 1, 2003; 77(4): 826 - 833. [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]
|
|
|
|
|
|
A. de Bree, W. M. Verschuren, A.-L. Bjorke-Monsen, N. M. van der Put, S. G Heil, F. J. Trijbels, and H. J Blom Effect of the methylenetetrahydrofolate reductase 677C->T mutation on the relations among folate intake and plasma folate and homocysteine concentrations in a general population sample Am. J. Clinical Nutrition, March 1, 2003; 77(3): 687 - 693. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. B. Mason Biomarkers of Nutrient Exposure and Status in One-Carbon (Methyl) Metabolism J. Nutr., March 1, 2003; 133(3): 941S - 947. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Orio Jr., S. Palomba, S. Di Biase, A. Colao, L. Tauchmanova, S. Savastano, D. Labella, T. Russo, F. Zullo, and G. Lombardi Homocysteine Levels and C677T Polymorphism of Methylenetetrahydrofolate Reductase in Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., February 1, 2003; 88(2): 673 - 679. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. C. Rampersaud, G. P.A. Kauwell, and L. B. Bailey Folate: A Key to Optimizing Health and Reducing Disease Risk in the Elderly J. Am. Coll. Nutr., February 1, 2003; 22(1): 1 - 8. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Crowther and J. G. Kelton Congenital Thrombophilic States Associated with Venous Thrombosis: A Qualitative Overview and Proposed Classification System Ann Intern Med, January 21, 2003; 138(2): 128 - 134. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Meleady, P. M Ueland, H. Blom, A. S Whitehead, H. Refsum, L. E Daly, S. E. Vollset, C. Donohue, B. Giesendorf, I. M Graham, et al. Thermolabile methylenetetrahydrofolate reductase, homocysteine, and cardiovascular disease risk: the European Concerted Action Project Am. J. Clinical Nutrition, January 1, 2003; 77(1): 63 - 70. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Yang and J D. Erickson Influence of reporting error on the relation between blood folate concentrations and reported folic acid-containing dietary supplement use among reproductive-aged women in the United States Am. J. Clinical Nutrition, January 1, 2003; 77(1): 196 - 203. [Abstract] [Full Text] [PDF]
|
|