Hostname: page-component-78c5997874-t5tsf Total loading time: 0 Render date: 2024-11-05T21:13:28.922Z Has data issue: false hasContentIssue false
  • English
  • Français

No association between common polymorphisms in genes of folate and homocysteine metabolism and the risk of Down's syndrome among French mothers

Published online by Cambridge University Press:  08 March 2007

Abalo Chango ,
Nathalie Fillon-Emery ,
Clotilde Mircher ,
Henri Bléhaut ,
Daniel Lambert ,
Bernard Herbeth ,
S. Jill James ,
Marie-Odile Réthoré  and
Jean Pierre Nicolas
Abalo Chango*
Affiliation:
INSERM U 724, Laboratory of Nutritional Genomics, ISAB – Agrohealth, Rue Pierre Waguet, 60 026 - Beauvais, France
Nathalie Fillon-Emery
Affiliation:
INSERM U 724, Laboratory of Medical Biochemistry, Faculty of Medicine, Vandoeuvre-lès-Nancy, France
Clotilde Mircher
Affiliation:
Jerome Lejeune Institute, Paris, France
Henri Bléhaut
Affiliation:
Jerome Lejeune Institute, Paris, France
Daniel Lambert
Affiliation:
INSERM U525, Nancy, France
Bernard Herbeth
Affiliation:
INSERM U525, Nancy, France
S. Jill James
Affiliation:
Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock AR, USA
Marie-Odile Réthoré
Affiliation:
Jerome Lejeune Institute, Paris, France
Jean Pierre Nicolas
Affiliation:
INSERM U 724, Laboratory of Medical Biochemistry, Faculty of Medicine, Vandoeuvre-lès-Nancy, France
*
*Corresponding author: Dr Abalo Chango, fax +33 344 06 2526, email [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

The cause of the non-disjunction leading to trisomy 21 remains unclear. Recent evidence has suggested that 5, 10-methylenetetrahydrofolate reductase (MTHFR) and/or methionine synthase reductase (MTRR) might contribute to the maternal risk of trisomy 21. The purpose of the present study was to analyse these findings among the French population and to investigate whether common polymorphisms in genes of the folate and homocysteine pathway, including the MTHFR 677C>T, MTHFR 1298A>C, the methionine synthase (MTR) 2756A>G, the cystathionine β-synthase (CBS) 844Ins68 and the reduced folate carrier (RFC-1) 80G>A polymorphisms, contribute to the risk of trisomy 21. The risk was studied by analysing independent and combined genotypes in 119 case mothers and 119 control mothers. The MTHFR 677T, MTHFR 1298C, MTR2756G, MTRR66G, CBSIns68+ and the RFC-1 80G allele frequencies were not significantly different among French case mothers, compared with control mothers. The risk of having a child with trisomy 21 did not appear to be linked to polymorphisms in genes associated with folate and homocysteine metabolism.

Keywords

Down's syndromeFolatePolymorphismRisk
Type
Research Article
Information
British Journal of Nutrition , Volume 94 , Issue 2 , August 2005 , pp. 166 - 169
Copyright
Copyright © The Nutrition Society 2005

References

Al-Gazali, LI, Padmanabhan, R & Melnyk, S (2001) Abnormal folate metabolism and genetic polymorphism of the folate pathway in a child with Down syndrome and neural tube defect. Am J Med Genet 103, 128–132.CrossRefGoogle Scholar
Bailey, LB, Gregory, JF III (1999) Polymorphisms of methylenetetrahydrofolate reductase and other enzymes: metabolic significance, risks, and impact on folate requirement. J Nutr 129, 919–922.CrossRefGoogle ScholarPubMed
Barkai, G, Arbuzova, S, Berkenstadt, M, Heifetz, S & Cuckle, H (2003) Frequency of Down's syndrome and neural-tube defects in the same family. Lancet 361, 1331–1335.CrossRefGoogle ScholarPubMed
Boduroglu, K, Alanay, Y, Koldan, B & Tuncbilek, E (2004) Methylenetetrahydrofolate reductase polymorphisms as maternal risk for Down syndrome in Turkey. Am J Med Genet 15, 5–10.CrossRefGoogle Scholar
Bosco, P, Gueant-Rodriguez, RM, Anello, G, Barone, C, Namour, F, Caraci, F, Romano, A, Romano, C & Gueant, JL (2003) Methionine synthase (MTR) 2756 (A>G) polymorphism, double heterozygosity methionine synthase 2756 AG/methionine synthase reductase (MTRR) 66 AG, and elevated homocysteinemia are three risk factors for having a child with Down syndrome. Am J Med Genet 121A, 219–224.CrossRefGoogle Scholar
Chadefaux-Vekemans, B, Coude, M, Muller, F, Oury, JF, Chabli, A, Jais, J & Kamoun, P (2002) Methylenetetrahydrofolate reductase polymorphism in the etiology of Down syndrome. Pediatr Res 51, 766–767.CrossRefGoogle ScholarPubMed
Chango, A, Emery-Fillon, N, de Courcy, GP, Lambert, D, Pfister, M, Rosenblatt, DS & Nicolas, JP (2000 a) A polymorphism (80G- >A) in the reduced folate carrier gene and its associations with folate status and homocysteinemia. Mol Genet Metab 70, 310–315.CrossRefGoogle ScholarPubMed
Chango, A, Potier de Courcy, G & Boisson, F (2000 b) 5, 10-Methylenetetrahydrofolate reductase (MTHFR), common mutations, folate status, and plasma homocysteine in healthy French adults of the SU.VI.MAX cohort. Br J Nutr 84, 891–896.CrossRefGoogle ScholarPubMed
Christensen, B, Arbour, L, Tran, P, Leclerc, D, Sabbaghian, N, Platt, R, Gilfix, BM, Rosenblatt, DS, Gravel, RA, Forbes, P & Rozen, R (1999) Genetic polymorphisms in methylenetetrahydro-folate and methionine synthase, folate levels in red blood cells, and risk of neural tube defects. Am J Med 84, 151–157.Google Scholar
da Silva, LRJ, Vergani, N, Galdieri, LC, Porto, MPR, Longhitano, SB, Brunoni, D, d'Almeida, V & Perez, ABA (2005) Relationship between polymorphisms in genes involved in homocysteine metabolism and maternal risk for Down syndrome in Brazil. Am J Med Genet 135, 263–267.CrossRefGoogle ScholarPubMed
Frosst, P, Blom, HJ & Milos, R (1995) A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 10, 111–113.CrossRefGoogle ScholarPubMed
Grillo, LB, Acacio, GL, Barini, R, Pinto, W Jr & Bertuzzo, CS (2002) Mutations in the methylenetetrahydrofolate reductase gene and Down syndrome. Cad Saude Publica 18, 1795–1797.CrossRefGoogle ScholarPubMed
Guéant, JL, Rodriguez-Guéant, RM, Anello, G, Bosco, P, Brunaud, L, Romano, C, Ferri, R, Romano, A, Candoto, M & Namour, B (2003) Genetic determinants of folates and vitamin B 12 metabolisms: a common pathway in neural tube defect and Down syndrome. Clin Chem Lab Med 41, 1473–1477.CrossRefGoogle ScholarPubMed
Hobbs, CA, Sherman, SL, Yi, P, Hopkins, SE, Torfs, CP, Hine, RJ, Pogribna, M, Rozen, R & James, SJ (2000) Polymorphisms in genes involved in folate metabolism as maternal risk factors for Down syndrome. Am J Hum Genet 67, 623–630.CrossRefGoogle ScholarPubMed
James, SJ (2004) Maternal metabolic phenotype and risk of Down syndrome: beyond genetics. Am J Med Genet 127A, 1–4.CrossRefGoogle Scholar
James, SJ & Hobbs, C (2002) Folate deficiency and molecular determinants of chromosome instability. In Folate and Human Development, pp. 43–69[Massaro, E and Rogers, JM, editors]. Totowa, NJ: Humana Press.CrossRefGoogle Scholar
James, SJ, Pogribna, M & Pogribny, IP, et al. (1999) Abnormal folate metabolism and mutation in the methylenetetrahydrofolate reductase gene may be maternal risk factors for Down syndrome. Am J Clin Nutr 70, 495–501.CrossRefGoogle ScholarPubMed
Lamb, NE, Feingold, E & Savage, A (1997) Characterization of susceptible chiasma configurations that increase the risk for maternal nondisjunction of chromosome 21. Hum Mol Genet 6, 1391–1399.CrossRefGoogle ScholarPubMed
Lejeune, J, Gautier, M & Turpin, MR (1959) Etude des chromosomes somatiques de neuf enfants mongoliens (Study of the somatic chromosomes of nine mongol children). C R Acad Sci (Paris) 248, 1721.Google Scholar
McKim, KS & Hawley, RS (1995) Chromosomal control of meiotic cell division. Science 270, 1595–1601.CrossRefGoogle ScholarPubMed
Morin, I, Devlin, AM, Leclerc, D, Sabbaghian, N, Halsted, CH, Finnell, R & Rozen, R (2003) Evaluation of genetic variants in the reduced folate carrier and in glutamate carboxypeptidase II for spina bifida risk. Mol Genet Metab 79, 197–200.CrossRefGoogle ScholarPubMed
O'Leary, VB, Parle-McDermott, A, Molloy, AM, Kirke, PN, Johnson, Z, Conley, M, Scott, JM & Mills, JL (2002) MTRR and MTHFR polymorphism: link to Down syndrome?. Am J Med Genet 107, 151–155.CrossRefGoogle ScholarPubMed
Sheth, JJ & Sheth, FJ (2003) Gene polymorphism and folate metabolism: a maternal risk factor for Down syndrome. Indian Pediatr 40, 115–123.Google ScholarPubMed
Stuppia, L, Gatta, V, Gaspari, AR, Antonucci, I, Morizio, E, Calabresse, G & Palka, G (2002) C677T mutation in the 5, 10-MTHFR gene and risk of Down syndrome in Italy. Eur J Hum Genet 10, 388–390.CrossRefGoogle ScholarPubMed
Tsai, MY, Bignell, M, Schwichtenberg, K & Hanson, NQ (1996) High prevalence of a mutation in the cystathionine beta-synthase gene. Am J Hum Genet 59, 1262–1267.Google ScholarPubMed
van der Put, NM, Gabreels, F, Stevens, EM, Smeitink, JA, Trijbels, FJ, Eskes, TK, van den Heuvel, LP & Blom, HJ (1998) A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects? Am J Hum Genet 62, 1044–1051.CrossRefGoogle ScholarPubMed
van der Put, NM, van der Molen, EF, Kluijtmans, LA, Heil, SG, Trijbels, JM, Eskes, TK, Van Oppenraaij-Emmerzaal, D, Banerjee, R & Blom, HJ (1997) Sequence analysis of the coding region of human methionine synthase: relevance to hyperhomocysteinaemia in neural-tube defects and vascular disease. Qjm 90, 511–517.CrossRefGoogle ScholarPubMed
Wilson, A, Platt, R, Wu, Q, Leclerc, D, Christensen, B, Yang, H, Gravel, RA & Rozen, R (1999) A common variant in methionine synthase reductase combined with low cobalamin (vitamin B12) increases risk for spina bifida. Mol Genet Metab 67, 317–323.CrossRefGoogle ScholarPubMed