Genetic polymorphisms in methylenetetrahydrofolate reductase and methionine synthase, folate levels in red blood cells, and risk of neural tube defects

American Journal of Medical Genetics

Volumn 84, Issue 2, 1999, Pages 151-157

  Christensen, Benedicte ^a,c   Arbour, Laura ^a,d   Tran, Pamela ^a   Leclerc, Daniel ^a   Sabbaghian, Nelly ^a   Platt, Robert ^a   Gilfix, Brian M ^a   Rosenblatt, David S ^a   Gravel, Roy A ^a   Forbes, Patricia ^a   Rozen, Rima ^a,b  

^a MCGILL UNIVERSITY HEALTH CENTRE   (Canada)

^b RESEARCH INSTITUTE OF THE MCGILL UNIVERSITY HEALTH CENTRE   (Canada)

^c Institute of Medical Genetics   (Norway)

^d UNIVERSITY OF BRITISH COLUMBIA   (Canada)

Author keywords

Folate; Homocysteine; Methionine synthase; Methylenetetrahydrofolate reductase; Neural tube defects

Indexed keywords

5,10 METHYLENETETRAHYDROFOLATE REDUCTASE (FADH2); FOLIC ACID; METHIONINE SYNTHASE;

ADOLESCENT; ADULT; ARTICLE; CELL LEVEL; CHILD; CONTROLLED STUDY; ERYTHROCYTE; FOLATE METABOLISM; GENETIC POLYMORPHISM; GENETIC RISK; HUMAN; HUMAN CELL; MAJOR CLINICAL STUDY; NEURAL TUBE DEFECT; PRESCHOOL CHILD; PRIORITY JOURNAL; RISK ASSESSMENT; SCHOOL CHILD;

5-METHYLTETRAHYDROFOLATE-HOMOCYSTEINE S-METHYLTRANSFERASE; ADOLESCENT; ADULT; CHILD; CHILD, PRESCHOOL; ERYTHROCYTES; FEMALE; FOLIC ACID; GENOTYPE; HOMOCYSTEINE; HUMANS; INFANT; MALE; METHYLENETETRAHYDROFOLATE REDUCTASE (NADPH2); MIDDLE AGED; NEURAL TUBE DEFECTS; OXIDOREDUCTASES ACTING ON CH-NH GROUP DONORS; POLYMORPHISM, GENETIC; POLYMORPHISM, RESTRICTION FRAGMENT LENGTH; PREVALENCE; RISK; VITAMIN B 12;

EID: 0032937206     PISSN: 01487299     EISSN: None     Source Type: Journal    
DOI: 10.1002/(SICI)1096-8628(19990521)84:2<151::AID-AJMG12>3.0.CO;2-T     Document Type: Article

References (40)

1. Bagley PJ, Selhub J. 1998. A common mutation in the methylenetetrahydrofolate reductase gene is associated with an accumulation of formylated tetrahydrofolates in red blood cells. Proc Natl Acad Sci USA 95:13217-13220.
2. Chen LH, Liu M-L, Hwang H-Y, Chen L-S, Korenberg J, Shane B. 1997. Human methionine synthase. cDNA cloning, gene localization and expression. J Biol Chem 272:3628-3634.
3. Christensen B, Frosst P, Lussier-Cacan S, Selhub J, Goyette P, Rosenblatt DS, Genest J Jr, Rozen R. 1997. Correlation of a common mutation in the methylenetetrahydrofolate reductase gene with plasma homocysteine in patients with premature coronary artery disease. Atheroscler Thromb Vase Biol 17:569-573.
4. Czeizel A, Dudas I. 1992. Prevention of the first occurrence of neural tube defects by periconceptional vitamin supplementation. N Engl J Med 327:1832-1835.
5. Daly LE, Kirke PN, Molloy A, Weir DG, Scott JM. 1995. Folate levels and neural tube defects: implications for prevention. JAMA 274:1698-1702.
6. Essien FB, Wannberg SL. 1993. Methionine but not folinic acid or vitamin B-12 alters the frequency of neural tube defects in Axd mutant mice. J Nutr 123:27-34.
7. Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, Boers GJH, den Heijer M, Kluijtmans LAJ, van den Heuvel LP, Rozen R. 1995. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 10:111-113.
8. Gilfix BM, Blank DW, Rosenblatt DS. 1997. Novel reductant for determination of total plasma homocysteine. Clin Chem 43:687-688.
9. Graf WD, Oleinik OE, Jack RM, Eder DN, Shurtleff DB. 1996. Plasma homocysteine and methionine concentrations in children with neural tube defects. Eur J Pediatr Surg 6(suppl I):7-9.
10. Harmon DL, Woodside JV, Yarnell JWG, McMaster D, Young IS, McCrum EE, Gey KF Whitehead AS, Evans AE. 1996. The common "thermolabile" variant of methylene tetrahydrofolate reductase is a major determinant of mild hyperhomocysteinaemia. Q J Med 89:571-577.
11. Herbert V. 1989. Development of human folate deficiency. In: Picciano MF, Stokstad ELR, Gregory JF II, editors. Folic acid metabolism in health and disease. New York: Wiley Liss, p 195-200.
12. 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.
13. 12 are independent risk factors for neural tube defects. Q J Med 86:703-708.
14. Kluijtmans LAJ, van den Heuvel LP, Boers GHJ, Frosst P, Stevens EMB, van Oost BA, den Heijer M, Trijbels FJM, Rozen R, Blom HJ. 1996. Molecular genetic analysis in mild hyperhomocysteinemia: a common mutation in the methylenetetrahydrofolate reductase gene is a genetic risk factor for cardiovascular disease. Am J Hum Genet 58:35-41.
15. Leclerc D, Campeau E, Goyette P, Adjalla CE, Christensen B, Ross M, Eydoux P, Rosenblatt DS, Rozen R, Gravel RA. 1996. Human methionine synthase: cDNA cloning, chromosomal localisation, and identification of mutations in patients of the cblG complementation group of folate/cobalamin disorders. Hum Mol Genet 5:1867-1874.
16. Li YN, Gulati S, Baker PJ, Brody LC, Banerjee R, Kruger WD. 1996. Cloning, mapping and RNA analysis of the human methionine synthase gene. Hum Mol Genet 5:1859-1865.
17. Mills JL, McPartlin JM, Kirke PN, Lee YJ, Conley MR, Weir DG, Scott JH. 1995. Homocysteine metabolism in pregnancies complicated by neural-tube defects. Lancet 345:149-151.
18. Mitchell LE, Duffy DL, Duffy P, Bellingham G, Martin NG. 1997. Genetic effects on variation in red-blood-cell folate in adults: implications for the familial aggregation of neural tube defects. Am J Hum Genet 60: 433-438.
19. Molloy AM, Daly S, Mills JL, Kirke PN, Whitehead AS, Ramsbottom D, Conley MR, Weir DG, Scott JM. 1997. Thermolabile variant of 5,10-methylenetetrahydrofolate reductase associated with low red-cell folates: implications for folate intake recommendations. Lancet 349: 1591-1593.
20. Molloy AM, Mills JL, Kirke PN, Whitehead AS, Weir DG, Scott JM. 1998a. Whole-blood folate values in subjects with different methylenetetrahydrofolate reductase genotypes: differences between the radioassay and microbiological assays. Clin Chem 44:186-188.
21. Molloy AM, Mills JL, Kirke PN, Ramsbottom D, McPartlin JM, Burke H, Conley M, Whitehead AS, Weir DG, Scott JM. 1998b. Low blood folates in NTD pregnancies are only partly explained by thermolabile 5,10-methylenetetrahydrofolate reductase: low folate status alone may be the critical factor. Am J Med Genet 78:155-159.
22. Morrison K, Edwards YH, Lynch SA, Burn H, Hol F, Mariman E. 1997. Methionine synthase and neural tube defects. J Med Genet 34:958-960.
23. MRC Vitamin Study Research Group. 1991. Prevention of neural tube defects: results of Medical Research Council Vitamin Study. Lancet 338:131-137.
24. Nelen WLDM, Steegers EAP, Eskes TKAB, Blom HJ. 1997. Genetic risk factor for unexplained recurrent early pregnancy loss. Lancet 350:861.
25. Ou CY, Stevenson RE, Brown VK, Schwartz CE, Allen WP, Khoury MJ, Rozen R, Oakley GP Jr, Adams MJ Jr. 1996. 5,10-Methylenetetrahydrofolate reductase genetic polymorphism as a risk factor for neural tube defects. Am J Med Genet 63:610-614.
26. Rosenquist TH, Ratashak SA, Selhub J. 1996. Homocysteine induces congenital defects of the heart and neural tube: effect of folic acid. Proc Natl Acad Sci USA 93:15227-15232.
27. Rozen R. 1997. Genetic predisposition to hyperhomocysteinemia: deficiency of methylenetetrahydrofolate reductase (MTHFR). Thromb Haemost 78:523-526.
28. Rozen R, Fraser FC, Shaw G. 1999. Decreased proportion of female new-borns homozygous for the 677 C→T mutation in methylenetetrahydrofolate reductase. Am J Med Genet (in press).
29. Shaw GM, Todoroff K, Finnell RH, Lammer EJ, Leclerc D, Gravel RA, Rozen, R. 1999. Infant methionine synthase variants and risk for spina bifida. J Med Genet 36:86-87.
30. Smithells RW, Sheppard S, Schorach CJ. 1976. Vitamin deficiencies and neural tube defects. Arch Dis Child 51:944-950.
31. Steegers-Theunissen RPM, Boers GHJ, Trijbels FJM, Finkelstein JD, Blom HJ, Thomas CMG, Borm GF, Wouters MGAJ, Eskes TKAB. 1994. Maternal hyperhomocysteinemia: a risk factor for neural tube defects? Metabolism 43:1475-1480.
32. van der Put NMJ, Steegers-Theunissen R, Frosst P, Trijbels FJM, Eskes TKAB, van den Heuvel LP, Mariman ECM, den Heyer M, Rozen R, Blom HJ. 1995. Mutated methylenetetrahydrofolate reductase as a risk factor for spina bifida. Lancet 346:1070-1071.
33. van der Put NMJ, van den Heuvel LP, Steegers-Theunissen RPM, Trijbels FJM, Eskes TKAB, Mariman ECM, den Heyer M, Blom HJ. 1996. Decreased methylenetetrahydrofolate reductase activity due to the 677C→T mutation in families with spina bifida offspring. J Mol Med 74:691-694.
34. van der Put NMJ, Eskes TKAB, Blom HJ. 1997a. Is the common 677 C→T mutation in the methylenetetrahydrofolate reductase gene a risk factor for neural tube defects? A meta-analysis. Q J Med 90:111-115.
35. van der Put NMJ, van der Molen EF, Kluijtmans LAJ, Heil SG, Trijbels JMF, Eskes TKAB, Van Oppenraaij-Emmerzaal D, Banerjee R, Blom HJ. 1997b. Sequence analysis of the coding region of human methionine synthase: relevance to hyperhomocysteinaemia in neural-tube defects and vascular disease. Q J Med 90:511-517.
36. Vilaseca MA, Moyano D, Ferrer I, Artuch R. 1997. Total homocysteine in pediatric patients. Clin Chem 43:690-692.
37. Weitkamp LR, Tackels DC, Hunter AGW, Holmes LB, Schwartz CE. 1998. Heterozygote advantage of the MTHFR gene in patients with neural-tube defect and their relatives. Lancet 351:1554-1555.
38. Whitehead AS, Gallagher P, Mills JL, Kirke PN, Burke H, Molloy AM, Weir DG, Shields DC, Scott JM. 1995. A genetic defect in 5,10 methylenetetrahydrofolate reductase in neural tube defects. Q J Med 88:763-766.
39. Wild J, Seller MJ, Schorach CJ, Smithells RW. 1994. Investigation of folate intake and metabolism in women who have had two neural tube defect pregnancies. Br J Obstet Gynaecol 101:197-202.
40. Yates JRW, Ferguson-Smith MA, Shenkin A, Guzman-Rodriguez R, White M, Clark BJ. 1987. Is disordered folate metabolism the basis for the genetic predisposition to neural tube defects? Clin Genet 31:274-287.