[1] Wagner C, Decha-Umphai W, Corbin J. Phosphorylation modulates the activity of glycine N-methyltransferase, a folate binding protein. In vitro phosphorylation is inhibited by the natural folate ligand. J Biol Chem1989;264(16):9638–42. [PubMed] [Google Scholar]
[2] Jencks DA, Mathews RG. Allosteric inhibition of methylenetetrahydrofolate reductase by adenosylmethionine. Effects of adenosylmethionine and NADPH on the equilibrium between active and inactive forms of the enzyme and on the kinetics of approach to equilibrium. J Biol Chem1987;262(6):2485–93. [PubMed] [Google Scholar]
[3] Wagner C, Briggs WT, Cook RJ. Inhibition of glycine N-methyltransferase activity by folate derivatives: implications for regulation of methyl group metabolism. Biochem Biophys Res Commun1985;127(3):746–52. [PubMed] [Google Scholar]
[4] Kutzbach C, Stokstad EL. Feedback inhibition of methylenetetrahydrofolate reductase in rat liver by S-adenosylmethionine. Biochim Biophys Acta1967;139(1):217–20. [PubMed] [Google Scholar]
[5] Townsend DM, Tew KD, Tapiero H. The importance of glutathione in human disease. Biomed Pharmacother2003;57(3–4):145–55. [PMC free article] [PubMed] [Google Scholar]
[6] Choi SW, Mason JB. Folate and carcinogenesis: an integrated scheme. J Nutr2000;130(2):129–32. [PubMed] [Google Scholar]
[7] Mason JB. Biomarkers of nutrient exposure and status in one-carbon (methyl) metabolism. J Nutr2003;133(Suppl 3):941S–7S. [PubMed] [Google Scholar]
[8] McCully KS. Vascular pathology of hom*ocysteinemia: implications for the pathogenesis of arteriosclerosis. Am J Pathol1969;56(1):111–28. [PMC free article] [PubMed] [Google Scholar]
[9] Clarke R, Daly L, Robinson K, Naughten E, Cahalane S, Fowler B, et al. Hyperhom*ocysteinemia: an independent risk factor for vascular disease. N Engl J Med1991;324(17):1149–55. [PubMed] [Google Scholar]
[10] Kang SS, Wong PWK, Malinow MR. Hyperhom*ocyst(e)inemia as a risk factor for occlusive vascular disease. Ann Rev Nutr1992;12:279–98. [PubMed] [Google Scholar]
[11] Vollset SE, Refsum H, Tverdal A, Nygard O, Nordrehaug JE, Tell GS, et al. Plasma total hom*ocysteine and cardiovascular and noncardiovascular mortality: the Hordaland hom*ocysteine Study.Am J Clin Nutr2001;74(1):130–6. [PubMed] [Google Scholar]
[12] McKusick VA. Heritable disorders of connective tissue. 3rd edSt. Louis: C.V. Mosby; 1966. p. 155. [Google Scholar]
[13] Ubbink JB, Vermaak WJ, van der Merwe A, Becker PJ. Vitamin B-12, vitamin B-6, and folate nutritional status in men with hyperhom*ocysteinemia. Am J Clin Nutr1993;57(1):47–53. [PubMed] [Google Scholar]
[14] Jacques PF, Selhub J, Bostom AG, Wilson PW, Rosenberg IH. The effect of folic acid fortification on plasma folate and total hom*ocysteine concentrations. N Engl J Med1999;340(19):1449–54. [PubMed] [Google Scholar]
[15] Riddell LJ, Chisholm A, Williams S, Mann JI. Dietary strategies for lowering hom*ocysteine concentrations. Am J Clin Nutr2000;71(6): 1448–54. [PubMed] [Google Scholar]
[16] Carson NA. Metabolic abnormalities detected in a survey of mentally backward individuals in Northern Ireland. Arch Dis Child1962;37: 505–13. [PMC free article] [PubMed] [Google Scholar]
[17] Gerritsen T, Vaughn JG, Waisman HA. The identification of hom*ocystine in the urine. Biochem Biophys Res Commun1962;9:493–6. [PubMed] [Google Scholar]
[18] Mudd SH, Skovby F, Levy HL, Pettigrew KD, Wilcken B, Pyeritz RE, et al. The natural history of hom*ocystinuria due to cystathionine beta-synthase deficiency. Am J Hum Genet1985;37(1):1–31. [PMC free article] [PubMed] [Google Scholar]
[19] Fowler B, Kraus J, Packman S, Rosenberg LE. hom*ocystinuria. Evidence for three distinct classes of cystathionine beta-synthase mutants in cultured fibroblasts. J Clin Invest1978;61(3):645–53. [PMC free article] [PubMed] [Google Scholar]
[20] Skovby F, Krassikoff N, Francke U. Assignment of the gene for cystathionine beta-synthase to human chromosome 21 in somatic cell hybrids. Hum Genet1984;65(3):291–4. [PubMed] [Google Scholar]
[21] Munke M, Kraus JP, Ohura T, Francke U. The gene for cystathionine beta-synthase (CBS) maps to the subtelomeric region on human chromosome 21q and to proximal mouse chromosome 17. Am J Hum Genet1988;42(4):550–9. [PMC free article] [PubMed] [Google Scholar]
[22] Kraus JP, Oliveriusova J, Sokolova J, Kraus E, Vlcek C, de Fran-chis R, et al. The human cystathionine beta-synthase (CBS) gene: complete sequence, alternative splicing, and polymorphisms. Genomics1998;52(3):312–24. [PubMed] [Google Scholar]
[23] Kraus JP, Janosik M, Kozich V, Mandell R, Shih V, Sperandeo MP, et al. Cystathionine beta-synthase mutations in hom*ocystinuria. Hum Mutat1999;13(5):362–75. [PubMed] [Google Scholar]
[24] Kraus JP. Komrower lecture. Molecular basis of phenotype expression in hom*ocystinuria. J Inherit Metab Dis1994;17(4):383–90. [PubMed] [Google Scholar]
[25] Abbott MH, Folstein SE, Abbey H, Pyeritz RE. Psychiatric manifestations of hom*ocystinuria due to cystathionine beta-synthase deficiency: prevalence, natural history, and relationship to neurologic impairment and vitamin B6-responsiveness. Am J Med Genet1987; 26(4):959–69. [PubMed] [Google Scholar]
[26] Frimpter GW. Cystathioninuria: nature of the defect. Science1965; 149(688):1095–6. [PubMed] [Google Scholar]
[27] Wong LT, Hardwick DF, Applegarth DA, Davidson AG. Review of metabolic screening program of children’s hospital, Vancouver, British Columbia. 1971–1977. Clin Biochem1979;12(5):167–72. [PubMed] [Google Scholar]
[28] Smith AJ, Strang LB. An inborn error of metabolism with the urinary excretion of alpha-hydroxy-butyric acid and phenylpyruvic acid.Arch Dis Child1958;33:109–13. [PMC free article] [PubMed] [Google Scholar]
[29] Tapiero H, Tew KD, Gaté L, Machover D. Prevention of pathologies associated with oxidative stress and dietary intake deficiencies: folate deficiency and requirements. Biomed Pharmacother2001;55:381–90. [PubMed] [Google Scholar]
[30] Luhby AL, Cooperman JM, Pesci-Bourel A. A new inborn error of metabolism: folic acid responsive megaloblastic anemia, ataxia, mental retardation, and convulsions. J Pediat1965;67:1052 [Google Scholar]
[31] Lanzkowsky P, Erlandson ME, Bezan AI. Isolated defect of folic acid absorption associated with mental retardation and cerebral calcification. Blood1969;34(4):452–65. [PubMed] [Google Scholar]
[32] Wollaston WH. On cystic oxide, a new species of urinary calculus. Phil Trans Roy Soc Lond1810;100:223–30. [Google Scholar]
[33] Calonge MJ, Gasparini P, Chillaron J, Chillon M, Gallucci M, Rou-saud F, et al. Cystinuria caused by mutations in rBAT, a gene involved in the transport of cystine. Nat Genet1994;6(4):420–5. [PubMed] [Google Scholar]
[34] Lee WS, Wells RG, Sabbag RV, Mohandas TK, Hediger MA. Cloning and chromosomal localization of a human kidney cDNA involved in cystine, dibasic, and neutral amino acid transport. J Clin Invest1993; 91(5):1959–63. [PMC free article] [PubMed] [Google Scholar]
[35] Feliubadalo L, Font M, Purroy J, Rousaud F, Estivill X, Nunes V, et al. Non-type I cystinuria caused by mutations in SLC7A9, encoding a subunit (bo+AT) of rBAT. International Cystinuria Consortium. Nat Genet1999;23(1):52–7. [PubMed] [Google Scholar]
[36] Leclerc D, Wilson A, Dumas R, Gafuik C, Song D, Watkins D, et al. Cloning and mapping of a cDNA for methionine synthase reductase, a flavoprotein defective in patients with hom*ocystinuria. Proc Natl Acad Sci USA1998;95(6):3059–64. [PMC free article] [PubMed] [Google Scholar]
[37] Wilson A, Leclerc D, Rosenblatt DS, Gravel RA. Molecular basis for methionine synthase reductase deficiency in patients belonging to the cblE complementation group of disorders in folate/cobalamin metabolism. Hum Mol Genet1999;8(11):2009–16. [PubMed] [Google Scholar]
[38] Wilson A, Platt R, Wu Q, Leclerc D, Christensen B, Yang H, et al. A common variant in methionine synthase reductase combined with low cobalamin (vitamin B12) increases risk for spina bifida. Molec Genet Metab1999;67:317–23. [PubMed] [Google Scholar]
[39] Hobbs CA, Sherman SL, Yi P, Hopkins SE, Torfs CP, Hine RJ, et al. Polymorphisms in genes involved in folate metabolism as maternal risk factors for Down syndrome. Am J Hum Genet2000;67(3):623–30. [PMC free article] [PubMed] [Google Scholar]
[40] James SJ, Pogribna M, Pogribny IP, Melnyk S, Hine RJ, Gibson JB, et al. Abnormal folate metabolism and mutation in the methylenetetrahydrofolate reductase gene may be maternal risk factors for Down syndrome. Am J Clin Nutr1999;70(4):495–501. [PubMed] [Google Scholar]
[41] Doolin MT, Barbaux S, McDonnell M, Hoess K, Whitehead AS, Mitchell LE. Maternal genetic effects, exerted by genes involved in hom*ocysteine remethylation, influence the risk of spina bifida. Am J Hum Genet2002;71(5):1222–6. [PMC free article] [PubMed] [Google Scholar]
[42] Gaughan DJ, Barbaux S, Kluijtmans LA, Whitehead AS. The human and mouse methylenetetrahydrofolate reductase (MTHFR) genes: genomic organization, mRNA structure and linkage to the CLCN6 gene. Gene2000;257(2):279–89. [PubMed] [Google Scholar]
[43] Sibani S, Christensen B, O’Ferrall E, Saadi I, Hiou-Tim F, Rosenblatt DS, et al. Characterization of six novel mutations in the methylenetetrahydrofolate reductase (MTHFR) gene in patients with hom*ocystinuria. Hum Mutat2000;15(3):280–7. [PubMed] [Google Scholar]
[44] Rozen RMolecular genetics of methylenetetrahydrofolate reductase deficiency. J Inherit Metab Dis1996;19(5):589–94. [PubMed] [Google Scholar]
[45] Goyette P, Sumner JS, Milos R, Duncan AM, Rosenblatt DS, Matthews RG, et al. Human methylenetetrahydrofolate reductase: isolation of cDNA, mapping and mutation identification. Nat Genet1994; 7(2):195–200. [PubMed] [Google Scholar]
[46] Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet1995;10(1):111–3. [PubMed] [Google Scholar]
[47] Schneider JA, Rees DC, Liu YT, Clegg JB. Worldwide distribution of a common methylenetetrahydrofolate reductase mutation. Am J Hum Genet1998;62(5):1258–60. [PMC free article] [PubMed] [Google Scholar]
[48] McAndrew PE, Brandt JT, Pearl DK, Prior TW. The incidence of the gene for thermolabile methylene tetrahydrofolate reductase in African Americans. Thromb Res1996;83(2):195–8. [PubMed] [Google Scholar]
[49] Bragley PJ, Selhub J. A common mutation in the methylenetetrahydrofolate reductase gene is associated with an accumulation of formylated tetrahydrofolates in red blood cells. Proc Natl Acad Sci USA1998;95:13217–20. [PMC free article] [PubMed] [Google Scholar]
[50] Friso S, Choi SW, Girelli D, Mason JB, Dolnikowski GG, Bagley PJ, et al. A common mutation in the 5,10-methylenetetrahydrofolate reductase gene affects genomic DNA methylation through an interaction with folate status. Proc Natl Acad Sci USA2002;99(8):5606–11. [PMC free article] [PubMed] [Google Scholar]
[51] Jacques PF, Bostom AG, Williams RR, Ellison RC, Eckfeldt JH, Rosenberg IH, et al. Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma hom*ocysteine concentrations. Circulation1996;93(1):7–9. [PubMed] [Google Scholar]
[52] Kluijtmans LA, van den Heuvel LP, Boers GH, Frosst P, Stevens EM, van Oost BA, et al. Molecular genetic analysis in mild hyperhom*ocysteinemia: a common mutation in the methylenetetrahydrofolate reductase gene is a genetic risk factor for cardiovascular disease. Am J Hum Genet1996;58(1):35–41. [PMC free article] [PubMed] [Google Scholar]
[53] Klerk M, Verhoef P, Clarke R, Blom HJ, Kok FJ, Schouten EG. MTHFR 677C → T polymorphism and risk of coronary heart disease: a meta-analysis. JAMA2002;288(16):2023–31. [PubMed] [Google Scholar]
[54] Christensen B, Arbour L, Tran P, Leclerc D, Sabbaghian N, Platt R, et al. Genetic polymorphisms in methylenetetrahydrofolate reductase and methionine synthase, folate levels in red blood cells, and risk of neural tube defects. Am J Med Genet1999;84(2):151–7. [PubMed] [Google Scholar]
[55] Ou CY, Stevenson RE, Brown VK, Schwartz CE, Allen WP, Khoury MJ, et al. 5,10 Methylenetetrahydrofolate reductase genetic polymorphism as a risk factor for neural tube defects. Am J Med Genet1996;63(4):610–4. [PubMed] [Google Scholar]
[56] Mornet E, Muller F, Lenvoise-Furet A, Delezoide AL, Col JY, Simon-Bouy B, et al. Screening of the C677T mutation on the methylenetetrahydrofolate reductase gene in French patients with neural tube defects. Hum Genet1997;100(5–6):512–4. [PubMed] [Google Scholar]
[57] Speer MC, Worley G, Mackey JF, Melvin E, Oakes WJ, George TM. The thermolabile variant of methylenetetrahydrofolate reductase (MTHFR) is not a major risk factor for neural tube defect in American Caucasians. The NTD Collaborative Group. Neurogenetics1997; 1(2):149–50. [PubMed] [Google Scholar]
[58] Motulsky AG. Nutritional ecogenetics: hom*ocysteine-related arteriosclerotic vascular disease, neural tube defects, and folic acid. Am J Hum Genet1996;58(1):17–20. [PMC free article] [PubMed] [Google Scholar]
[59] Pietrzyk JJ, Bik-Multanowski M, Sanak M, Twardowska M. Polymorphisms of the 5,10-methylenetetrahydrofolate and the methionine synthase reductase genes as independent risk factors for spina bifida. J Appl Genet2003;44(1):111–3. [PubMed] [Google Scholar]
[60] Pogribna M, Melnyk S, Pogribny I, Chango A, Yi P, James SJ. hom*ocysteine metabolism in children with Down syndrome: in vitro modulation. Am J Hum Genet2001;69(1):88–95. [PMC free article] [PubMed] [Google Scholar]
[61] O’Leary VB, Parle-McDermott A, Molloy AM, Kirke PN, Johnson Z, Conley M, et al. MTRR and MTHFR polymorphism: link to Down syndrome?Am J Med Genet2002;107(2):151–5. [PubMed] [Google Scholar]
[62] Wisniewski KE, Wisniewski HM, Wen GY. Occurrence of neuropathological changes and dementia of Alzheimer’s disease in Down’s syndrome. Ann Neurol1985;17(3):278–82. [PubMed] [Google Scholar]
[63] Religa D, Styczynska M, Peplonska B, Gabryelewicz T, Pfeffer A, Chodakowska M, et al. hom*ocysteine, apolipoproteine E and methylenetetrahydrofolate reductase in Alzheimer’s disease and mild cognitive impairment. Dement Geriatr Cogn Disord2003;16(2):64–70. [PubMed] [Google Scholar]
[64] Hoffman RM. Methionine dependence in cancer cells—a review. In Vitro1982;18(5):421–8. [PubMed] [Google Scholar]
[65] Hoffman RM. Altered methionine metabolism and transmethylation in cancer. Anticancer Res1985;5(1):1–30. [PubMed] [Google Scholar]
[66] Liteplo RG, Hipwell SE, Rosenblatt DS, Sillaots S, Lue-Shing H. Changes in cobalamin metabolism are associated with the altered methionine auxotrophy of highly growth autonomous human melanoma cells. J Cell Physiol1991;149(2):332–8. [PubMed] [Google Scholar]
[67] Tautt JW,Anuszewska EL, Koziorowska JH. Methionine regulation of N-5-methyltetrahydrofolate: hom*ocysteine methyltransferase and its influence on the growth and protein synthesis in normal, neoplastic, and transformed cells in culture. J Natl Cancer Inst1982;69(1):9–14. [PubMed] [Google Scholar]
[68] Fiskerstrand T, Christensen B, Tysnes OB, Ueland PM, Refsum H. Development and reversion of methionine dependence in a human glioma cell line: relation to hom*ocysteine remethylation and cobalamin status. Cancer Res1994;54(18):4899–906. [PubMed] [Google Scholar]
[69] Tang B, Li YN, Kruger WD. Defects in methylthioadenosine phosphorylase are associated with but not responsible for methionine-dependent tumor cell growth. Cancer Res2000;60(19):5543–7. [PubMed] [Google Scholar]
[70] Matsuo K, Hamajima N, Hirai T, Kato T, Inoue M, Takezaki T, et al. Methionine synthase reductase gene A66G polymorphism is associated with risk of colorectal cancer.Asian Pac J Cancer Prev2002;3(4): 353–9. [PubMed] [Google Scholar]
[71] Paz MF, Avila S, Fraga MF, Pollan M, Capella G, Peinado MA, et al. Germ-line variants in methyl-group metabolism genes and susceptibility to DNA methylation in normal tissues and human primary tumors. Cancer Res2002;62(15):4519–24. [PubMed] [Google Scholar]
[72] Skibola CF, Smith MT, Kane E, Roman E, Rollinson S, Cart-wright RA, et al. Polymorphisms in the methylenetetrahydrofolate reductase gene are associated with susceptibility to acute leukemia in adults. Proc Natl Acad Sci USA1999;96(22):12810–5. [PMC free article] [PubMed] [Google Scholar]
[73] Wiemels JL, Smith RN, Taylor GM, Eden OB, Alexander FE, Greaves MF. Methylenetetrahydrofolate reductase (MTHFR) polymorphisms and risk of molecularly defined subtypes of childhood acute leukemia. Proc Natl Acad Sci USA2001;98(7):4004–9. [PMC free article] [PubMed] [Google Scholar]
