This article was prepared by a group consisting of both United States Government employees and non-United States Government employees, and as such is subject to 117 U.S.C. Sec. 105.
Article first published online: 28 NOV 2001
Copyright Published 2001 Wiley-Liss, Inc.
American Journal of Medical Genetics
Volume 107, Issue 2, pages 151–155, 15 January 2002
How to Cite
O'Leary, V. B., Parle-McDermott, A., Molloy, A. M., Kirke, P. N., Johnson, Z., Conley, M., Scott, J. M. and Mills, J. L. (2002), MTRR and MTHFR polymorphism: Link to Down syndrome?. Am. J. Med. Genet., 107: 151–155. doi: 10.1002/ajmg.10121
Zachary Johnson is deceased.
- Issue published online: 18 DEC 2001
- Article first published online: 28 NOV 2001
- Manuscript Accepted: 13 SEP 2001
- Manuscript Received: 20 DEC 2000
- Health Research Board of Ireland
- National Institute of Child Health and Human Development
- Biomed. Grant Number: 983549
- methionine synthase reductase;
- methylenetetrahydrofolate reductase;
- Down syndrome;
- MTRR A66G;
- MTHFR C677T mutation;
- trisomy 21
Polymorphisms in genes encoding the folate metabolizing enzymes methylenetetrahydrofolate reductase (MTHFR C677T) and methionine synthase reductase (MTRR A66G) have been linked to the etiology of Down syndrome. We examined the prevalence of these variant genotypes in mothers who had given birth to a child with Down syndrome (n = 48) and in control mothers (n = 192), and investigated the biochemical factors influenced by the presence of MTRR A66G and MTHFR C677T. The frequency of the MTRR variant genotypes (AG, GG) was significantly higher in mothers of children with Down syndrome compared to controls (P = 0.0028). MTHFR C677T genotype frequencies were not significantly altered in mothers of children with Down syndrome (P = 0.74). However, mothers who had a MTHFR CT or TT genotype and a MTRR GG genotype had a 2.98-fold increased risk of having a child with Down syndrome (P = 0.02). The MTRR polymorphism did not increase plasma homocysteine. Higher homocysteine was found with the presence of the MTHFR T allele. In conclusion, MTRR A66G is significantly more common in mothers of children with Down syndrome but does not appear to increase the risk for Down syndrome by changing homocysteine metabolism. Women who have both the MTRR and MTHFR variant genotypes are also at increased risk of producing offspring with Down syndrome. Published 2001 Wiley-Liss, Inc.