Modulation of the homocysteine-betaine relationship by methylenetetrahydrofolate reductase 677 C->T genotypes and B-vitamin status in a large-scale epidemiological study

Journal of Clinical Endocrinology and Metabolism

Volumn 92, Issue 4, 2007, Pages 1535-1541

  Holm, Pål I ^a   Hustad, Steinar ^a   Ueland, Per Magne ^b   Vollset, Stein Emil ^b   Grotmol, Tom ^c   Schneede, Jørn ^b  

^a HAUKELAND UNIVERSITY HOSPITAL   (Norway)

^b UNIVERSITY OF BERGEN   (Norway)

^c CANCER REGISTRY OF NORWAY   (Norway)

Author keywords

[No Author keywords available]

Indexed keywords

BETAINE; CHOLINE; CYANOCOBALAMIN; DIMETHYLGLYCINE; FOLIC ACID; HOMOCYSTEINE; METHYLENETETRAHYDROFOLATE REDUCTASE (NADPH2); PYRIDOXINE; RIBOFLAVIN; VITAMIN B GROUP;

ADULT; ARTICLE; BLOOD ANALYSIS; BLOOD SAMPLING; CONTROLLED STUDY; FEMALE; GENOTYPE; HUMAN; MALE; NORMAL HUMAN; OUTCOME ASSESSMENT; PRIORITY JOURNAL;

EID: 34147162422     PISSN: 0021972X     EISSN: 0021972X     Source Type: Journal    
DOI: 10.1210/jc.2006-1471     Document Type: Article

References (42)

1. De Bree A, Verschuren WMM, Kromhout D, Kluijtmans LAJ, Blom HJ 2002 Homocysteine determinants and the evidence to what extent homocysteine determines the risk of coronary heart disease. Pharmacol Rev 54:599-618
2. Carmel R, Jacobsen D 2001 Homocysteine in health and disease. Cambridge, UK: Cambridge University Press
3. Refsum H, Ueland PM, Nygard O, Vollset SE 1998 Homocysteine and cardiovascular disease. Annu Rev Med 49:31-62
4. Wilcken DE, Wilcken B 1997 The natural history of vascular disease in homocystinuria and the effects of treatment. J Inherit Metab Dis 20:295-300
5. Brouwer IA, Verhoef P, Urgert R 2000 Betaine supplementation and plasma homocysteine in healthy volunteers. Arch Intern Med 160:2546-2547
6. Schwab U, Torronen A, Toppinen L, Alfthan G, Saarinen M, Aro A, Uusitupa M 2002 Betaine supplementation decreases plasma homocysteine concentrations but does not affect body weight, body composition, or resting energy expenditure in human subjects. Am J Clin Nutr 76:961-967
7. Steenge GR, Verhoef P, Katan MB 2003 Betaine supplementation lowers plasma homocysteine in healthy men and women. J Nutr 133:1291-1295
8. Olthof MR, Van Vliet T, Boelsma E, Verhoef P 2003 Low dose betaine supplementation leads to immediate and long term lowering of plasma homocysteine in healthy men and women. J Nutr 133:4135-4138
9. Alfthan G, Tapani K, Nissinen K, Saarela J, Aro A 2004 The effect of low doses of betaine on plasma homocysteine in healthy volunteers. Br J Nutr 92:665-669
10. Schwab U, Torronen A, Meririnne E, Saarinen M, Alfthan G, Aro A, Uusitupa M 2006 Orally administered betaine has an acute and dose-dependent effect on serum betaine and plasma homocysteine concentrations in healthy humans. J Nutr 136:34-38
11. Holm PI, Ueland PM, Vollset SE, Midttun O, Blom HJ, Keijzer MB, den Heijer M 2005 Betaine and folate status as cooperative determinants of plasma homocysteine in humans. Arterioscler Thromb Vasc Biol 25:379-385
12. Ueland PM, Holm PI, Hustad S 2005 Betaine: a key modulator of one-carbon metabolism and homocysteine status. Clin Chem Lab Med 43:1069-1075
13. Garrow T 2001 Betaine-dependent remethylation. In: Carmel R, Jacobsen D, eds. Homocysteine in health and disease. Cambridge, UK: Cambridge University Press
14. McKinley MC, McNulty H, McPartlin J, Strain JJ, Pentieva K, Ward M, Weir DG, Scott JM 2001 Low-dose vitamin B-6 effectively lowers fasting plasma homocysteine in healthy elderly persons who are folate and riboflavin replete. Am J Clin Nutr 73:759-764
15. Ubbink JB, van der Merwe A, Delport R, Allen RH, Stabler SP, Riezler R, Vermaak WJ 1996 The effect of a subnormal vitamin B-6 status on homocysteine metabolism. J Clin Invest 98:177-184
16. Selhub J, Miller JW 1992 The pathogenesis of homocysteinemia: interruption of the coordinate regulation by S-adenosylmethionine of the remethylation and transsulfuration of homocysteine. Am J Clin Nutr 55:131-138
17. Hustad S, Ueland PM, Vollset SE, Zhang Y, Bjorke-Monsen AL, Schneede J 2000 Riboflavin as a determinant of plasma total homocysteine: effect modification by the methylenetetrahydrofolate reductase C677T polymorphism. Clin Chem 46:1065-1071
18. Finkelstein JD 1990 Methionine metabolism in mammals. J Nutr Biochem 1:228-237
19. Pfeiffer CM, Fazili Z, McCoy L, Zhang M, Gunter EW 2004 Determination of folate vitamers in human serum by stable-isotope-dilution tandem mass spectrometry and comparison with radioassay and microbiologic assay. Clin Chem 50:423-432
20. Bailey LB, Gregory 3rd JF 1999 Polymorphisms of methylenetetrahydrofolate reductase and other enzymes: metabolic significance, risks and impact on folate requirement. J Nutr 129:919-922
21. Botto LD, Yang Q 2000 5,10-Methylenetetrahydrofolate reductase gene variants and congenital anomalies: a HuGE review. Am J Epidemiol 151:862-877
22. Kang SS, Wong PW, Susmano A, Sora J, Norusis M, Ruggie N 1991 Thermolabile methylenetetrahydrofolate reductase: an inherited risk factor for coronary artery disease. Am J Hum Genet 48:536-545
23. Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, Boers GJ, den Heijer M, Kluijtmans LA, van den Heuvel LP 1995 A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 10:111-113
24. Jacques PF, Bostom AG, Williams RR, Ellison RC, Eckfeldt JH, Rosenberg IH, Selhub J, Rozen R 1996 Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations. Circulation 93:7-9
25. Bretthauer M, Gondal G, Larsen K, Carlsen E, Eide TJ, Grotmol T, Skovlund E, Tveit KM, Vatn MH, Hoff G 2002 Design, organization and management of a controlled population screening study for detection of colorectal neoplasia: attendance rates in the NORCCAP study (Norwegian Colorectal Cancer Prevention). Scand J Gastroenterol 37:568-573
26. Gondal G, Grotmol T, Hofstad B, Bretthauer M, Eide TJ, Hoff G 2003 The Norwegian Colorectal Cancer Prevention (NORCCAP) screening study: baseline findings and implementations for clinical work-up in age groups 50-64 years. Scand J Gastroenterol 38:635-642
27. O'Broin S, Kelleher B 1992 Microbiological assay on microtitre plates of folate in serum and red cells. J Clin Pathol 45:344-347
28. Kelleher BP, Broin SD 1991 Microbiological assay for vitamin B12 performed in 96-well microtitre plates. J Clin Pathol 44:592-595
29. Windelberg A, Arseth O, Kvalheim G, Ueland PM 2005 Automated assay for the determination of methylmalonic acid, total homocysteine, and related amino acids in human serum or plasma by means of methylchloroformate derivatization and gas chromatography-mass spectrometry. Clin Chem 51:2103-2109
30. Midttun O, Hustad S, Solheim E, Schneede J, Ueland PM 2005 Multianalyte quantification of vitamin B6 and B2 species in the nanomolar range in human plasma by liquid chromatography-tandem mass spectrometry. Clin Chem 51:1206-1216
31. Holm PI, Ueland PM, Kvalheim G, Lien EA 2003 Determination of choline, betaine, and dimethylglycine in plasma by a high-throughput method based on normal-phase chromatography-tandem mass spectrometry. Clin Chem 49:286-294
32. Ulvik A, Ueland PM 2001 Single nucleotide polymorphism (SNP) genotyping in unprocessed whole blood and serum by real-time PCR: application to SNPs affecting homocysteine and folate metabolism. Clin Chem 47:2050-2053
33. Hastie T, Tibshirani R 1986 Generalized additive models. Stat Sci 297-310
34. R Development Core Team 2006 R: a language and environment for statistical computing. Vienna: R Foundation for Statistical Computing
35. Melse-Boonstra A, Holm PI, Ueland PM, Olthof M, Clarke R, Verhoef P 2005 Betaine concentration as a determinant of fasting total homocysteine concentrations and the effect of folic acid supplementation on betaine concentrations. Am J Clin Nutr 81:1378-1382
36. Lever M, Sizeland PC, Bason LM, Hayman CM, Chambers ST 1994 Glycine betaine and proline betaine in human blood and urine. Biochim Biophys Acta 1200:259-264
37. Brattstrom L, Wilcken DE, Ohrvik J, Brudin L 1998 Common methylenetetrahydrofolate reductase gene mutation leads to hyperhomocysteinemia but not to vascular disease: the result of a meta-analysis. Circulation 98:2520-2526
38. Niculescu MD, Zeisel SH 2002 Diet, methyl donors and DNA methylation: interactions between dietary folate, methionine and choline. J Nutr 132:2333S-2335S
39. Hustad S, Schneede J, Ueland PM 2005 Riboflavin and methylenetetrahydrofolate reductase. In: Ueland PM, Rozen R, eds. MTHFR polymorphisms and disease. Georgetown, Texas: Landes Bioscience/Eurekah; 71-77
40. Shimakawa T, Nieto FJ, Malinow MR, Chambless LE, Schreiner PJ, Szklo M 1997 Vitamin intake: a possible determinant of plasma homocyst(e)ine among middle-aged adults. Ann Epidemiol 7:285-293
41. Finkelstein JD, Martin JJ, Harris BJ 1988 Methionine metabolism in mammals. The methionine-sparing effect of cystine. J Biol Chem 263:11750-11754
42. Yamada K, Chen Z, Rozen R, Matthews RG 2001 Effects of common polymorphisms on the properties of recombinant human methylenetetrahydrofolate reductase. Proc Natl Acad Sci USA 98:14853-14858