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MTRR and MTHFR polymorphism: link to Down syndrome?
Valerie B O'Leary1, Anne Parle-McDermott, Anne M Molloy
1Department of Biochemistry, Trinity College, Dublin, Ireland.
American Journal of Medical Genetics
|January 25, 2002
Summary
The methionine synthase reductase (MTRR A66G) variant genotype is more common in mothers of children with Down syndrome. However, a combination of MTRR and methylenetetrahydrofolate reductase (MTHFR C677T) variant genotypes increases Down syndrome risk.
Area of Science:
- Genetics
- Human Biology
- Reproductive Health
Background:
- Polymorphisms in folate metabolizing enzymes are implicated in Down syndrome.
- Methylenetetrahydrofolate reductase (MTHFR C677T) and methionine synthase reductase (MTRR A66G) are key enzymes in folate metabolism.
Purpose of the Study:
- To investigate the prevalence of MTHFR C677T and MTRR A66G variant genotypes in mothers of children with Down syndrome.
- To explore the association between these genotypes and biochemical factors, including homocysteine levels.
Main Methods:
- Case-control study comparing genotype frequencies in mothers of children with Down syndrome (n=48) and control mothers (n=192).
- Analysis of biochemical factors influenced by MTRR A66G and MTHFR C677T genotypes.
Main Results:
- MTRR variant genotypes (AG, GG) were significantly more frequent in mothers of children with Down syndrome (P = 0.0028).
- MTHFR C677T genotype frequencies did not differ significantly between groups (P = 0.74).
- A combined MTHFR CT/TT and MTRR GG genotype showed a 2.98-fold increased risk for Down syndrome (P = 0.02).
- MTRR polymorphism did not affect plasma homocysteine; MTHFR T allele was associated with higher homocysteine.
Conclusions:
- MTRR A66G is more prevalent in mothers of children with Down syndrome but does not appear to alter homocysteine metabolism.
- Combined MTRR and MTHFR variant genotypes increase the risk of having a child with Down syndrome.