Abnormal folate metabolism and mutation in the methylenetetrahydrofolate reductase gene may be maternal risk factors for Down syndrome

American Journal of Clinical Nutrition

Volumn 70, Issue 4, 1999, Pages 495-501

  James, S Jill ^a   Pogribna, Marta ^b   Pogribny, Igor P ^b   Melnyk, Stepan ^b   Hine, R Jean ^b   Gibson, James B ^b   Yi, Ping ^b   Tafoya, Dixie L ^b   Swenson, David H ^b   Wilson, Vincent L ^b   Gaylor, David W ^b  

^a NATIONAL CENTER FOR TOXICOLOGICAL RESEARCH   (United States)

^b NONE

Author keywords

DNA methylation; Down syndrome; Folate; Homocysteine; Methylenetetrahydrofolate reductase; MTHFR 677C T mutation; Mutation; Trisomy 21

Indexed keywords

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

ADULT; AMINO ACID METABOLISM; AMINO ACID SUBSTITUTION; ANEUPLOIDY; ARTICLE; CHROMOSOME SEGREGATION; DNA METHYLATION; DOWN SYNDROME; DRUG EFFECT; EXTRACHROMOSOMAL INHERITANCE; FEMALE; GENE MUTATION; HUMAN; MAJOR CLINICAL STUDY; RISK FACTOR; TRISOMY 21;

EID: 0032845227     PISSN: 00029165     EISSN: None     Source Type: Journal    
DOI: 10.1093/ajcn/70.4.495     Document Type: Article

References (40)

1. Epstein CJ. Down syndrome (trisomy 21). In: Stansbury JB, Wyngarden JB, Fredrickson DS, eds. The metabolic and molecular bases of inherited disease. 7th ed. New York: McGraw-Hill, 1995:749-95.
2. Antofnarakis SE, Petersen MB, McInnis MG, et al. The meiotic stage of nondisjunction in trisomy 21: determination by using DNA polymorphisms. Am J Hum Genet 1992;50:544-50.
3. Hernandez D, Fisher EMC. Down syndrome genetics: unravelling a multifactorial disorder. Hum Mol Genet 1996;5:1411-6.
4. Ji WZ, Hernandez R, Zhang XY, et al. DNA demethylation and pericentromeric rearrangements of chromosome 1. Mutat Res 1997;379:33-41.
5. Jeanpierre M, Turleau C, Aurius A, et al. An embryonic-like methylation pattern of classical satellite DNA is observed in ICF syndrome. Hum Mol Genet 1993;2:731-5.
6. Harrison JJ, Anisowicz A, Gadi IG, Raffeld M, Sager R. Azacytidine-induced tumorigenesis of CHEF/18 cells: correlated DNA methylation and chromosome changes. Proc Natl Acad Sci U S A 1983;80:6606-10.
7. Leyton C, Mergudich D, de la Torre C, Sans J. Impaired chromosome segregation in plant anaphase after moderate hypomethylation of DNA. Cell Prolif 1995;28:481-96.
8. Lengauer C, Kinzler KW, Vogelstein B. DNA methylation and genetic instability in colorectal cancer cells. Proc Natl Acad Sci U S A 1997;94:2545-50.
9. Qu GZ, Grundy P, Narayan A, Ehrlich M. Frequent hypomethylation in Wilms tumors of pericentromeric DNA in chromosomes 1 and 16. Cancer Genet Cytogenet 1998;76:196-201.
10. Pogribny IP, Miller BJ, James SJ. Alterations in hepatic p53 gene methylation patterns during tumor progression with folate/methyl deficiency in the rat. Cancer Lett 1997;115:31-8.
11. Christman JK, Sheikhnejad G, Dizik M, Abileah S, Wainfan E. Reversibility of changes in nucleic acid methylation and gene expression induced in rat liver by severe dietary methyl deficiency. Carcinogenesis 1993;14:551-7.
12. Pogribny IP, Basnakian AG, Miller BJ, Lopatina NG, Poirier LA, James SJ. Breaks in genomic DNA and within the p53 gene are associated with hypomethylation in livers of folate/methyl deficient rats. Cancer Res 1995;55:1894-901.
13. Pogribny IP, Muskhelishvili L, Miller BJ, James SJ. Presence and consequence of uracil in preneoplastic DNA from folate/methyl deficient rats. Carcinogenesis 1997;8:2071-6.
14. Wainfan E, Poirier LA. Methyl groups in carcinogenesis: effects on DNA methylation and gene expression. Cancer Res 1992;52:2071s-7s.
15. Frosst P, Blom HJ, Milos R, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 1995;10:111-3.
16. De Cabo SF, Hazen MJ, Molero ML, Fernández-Piqueras J. S-adenosyl-L-homocysteine: a non-cytotoxic hypomethylating agent. Experientia 1994;50:658-9.
17. Balaghi M, Wagner C. DNA methylation in folate deficiency - use of CpG methylase. Biochem Biophys Res Commun 1993;193:1184-90.
18. Block G, Hartman AM, Dresser CM, Carroll MD, Gannon J, Gardener L. A data-based approach to diet questionnaire design and testing. Am J Epidemiol 1986;139:1190-6.
19. Ausebel FM, Brent R, Kingston RE, Moore DD, Seidman JG, Smith JA. In: Current protocols in molecular biology. New York: Wiley-Interscience, 1989:2.3.1-2.3.3.
20. Chen J, Giovannucci E, Kelsey K, et al. A methylenetetrahydrofolate reductase polymorphism and the risk of colorectal cancer. Cancer Res 1996;56:4862-4.
21. Melnyk S, Pogribna M, Pogribny IP, Hine RJ, James SJ. A new HPLC method for the simultaneous determination of oxidized and reduced plasma aminothiols using coulometric electrochemical detection. Nutr Biochem 1999 (in press).
22. Broxson EH Jr, Stork LC, Allen RH, Stabler SP, Kolhouse JF. Changes in plasma methionine and total homocysteine levels in patients receiving methotrexate infusions. Cancer Res 1989;49:5879-83.
23. Freeman S, Grantham M, Hassold T, et al. Cytogenetic and molecular studies of spontaneous human abortions. Am J Hum Genet 1996;49(suppl):916A(abstr).
24. Lamb NE, Feingold E, Savage A, et al. Characterization of susceptible chiasma configurations that increase the risk for maternal nondisjunction of chromosome 21. Hum Mol Genet 1997;6:1391-9.
25. Almeida A, Kokalj-Vokac N, Lefrancois D, et al. Hypomethylation of classical satellite DNA and chromosome instability in lymphoblastoid cell lines. Hum Genet 1993;91:538-46.
26. Hernandez R, Frady A, Zhang XY, Varela M, Ehrlich M. Preferential induction of chromosome 1 multibranched figures and wholearm deletions in a human pro-B cell line treated with 5-azacytidine or 5-azadeoxycytidine. Cytogenet Cell Genet 1997;76:196-201.
27. Karpen GH, Allshire RC. The case for epigenetic effects on centromere identity and function. Trends Genet 1997;13:489-96.
28. De Cabo SF, Santos J, Fernández-Piqueras J. Molecular and cytological evidence of S-adenosyl-L-homocysteine as an innocuous undermethylating agent in vivo. Cytogenet Cell Genet 1995;71:187-92.
29. van der Put NMJ, Steegers-Theunissen RPM, Frosst P, et al. Mutated methylenetetrahydrofolate reductase as a risk factor for spina bifida. Lancet 1995;346:1070-1.
30. van der Put NM, Eskes TK, Blom HJ. Is the common 677C→T mutation in the methylenetetrahydrofolate reductase gene a risk factor for neural tube defects? A meta-analysis. Q J Med 1997;90:111-5.
31. 12 metabolism in families with spina bifida offspring. Q J Med 1998;62:1022-51.
32. Rozen R. Molecular genetics of methylenetetrahydrofolate reductase deficiency. J Inherit Metab Dis 1996;19:589-94.
33. Molloy A, Daly S, Mills JM, et al. Methylenetetrahydrofolate reductase associated with low red cell folates: implications for folate intake recommendations. Lancet 1997;349:1591-3.
34. Czeizel AE, Dudas I. Prevention of the first occurrence of neural tube defects by periconceptional vitamin supplementation. N Engl J Med 1992;327:1832-5.
35. MRC Vitamin Study Research Group. Folic acid and the prevention of neural tube defects: results of the Medical Council Vitamin Study. Lancet 1991;338:131-7.
36. Motulsky AG. Nutritional ecogenetics: homocysteine-related arteriosclerotic vascular disease, neural tube defects, and folic acid. Am J Hum Genet 1996;58:17-20.
37. Rosen R. Genetic predisposition to hyperhomocysteinemia: deficiency of methylene tetrahydrofolate reductase (MTHFR). Thromb Haemost 1997;78:523-6.
38. Canfield MA, Annegers JF, Brender JD, Cooper SP, Greenberg F. Hispanic origin and neural tube defects in Houston/Harris County, Texas. Am J Epidemiol 1996;43:12-24.
39. Strassburg MA, Greenland S, Portigal LD, Sever LE. A population-based case-control study of anencephalus and spina bifida in a low-risk area. Dev Med Child Neurol 1983;25:632-41.
40. Down syndrome prevalence at birth - United States, 1983-1990. Teratology 1997;56:31-6.