Abstract |
The methionine synthase reductase (MTRR) enzyme restores methionine synthase (MTR) enzyme activity and therefore plays an essential role in homocysteine remethylation. In some studies, the 66A>G polymorphism in the MTRR gene was associated with increased neural tube defect (NTD) risk. Using a case-control design, we studied the association between the MTRR 66A>G polymorphism and spina bifida risk in 121 mothers, 109 spina bifida patients, 292 control women, and 234 pediatric controls. Possible interactions between the MTRR 66A>G variant and the MTR 2756A>G polymorphism, the MTHFR 677C>T variant, plasma vitamin B12, and plasma methylmalonic acid (MMA) levels were examined in the 121 mothers and 292 control women. Meta-analyses were conducted to set the results of the case-control study in the context of eligible literature on the relation between the MTRR 66A>G variant and NTD risk. Finally, a transmission disequilibrium test was performed for 82 complete mother-father-child triads to test for preferential transmission of the MTRR risk allele. In our case-control study, the MTRR 66A>G polymorphism had no influence on spina bifida risk in children [odds ratio (OR) 0.6, 95% confidence interval (CI) 0.4-1.1]. The MTRR 66GG genotype increased maternal spina bifida risk by 2.1-fold (OR 2.1, 95% CI 1.3-3.3). This risk became more pronounced in combination with the MTHFR 677TT genotype (OR 4.0, 95% CI 1.3-12.5). Moreover, we demonstrate a possible interaction between the MTRR 66GG genotype and high plasma MMA levels (OR 5.5, 95% CI 2.2-13.5). The meta-analyses demonstrated that the maternal MTRR 66GG genotype was associated with an overall 55% (95% CI 1.04-2.30) increase in NTD risk and that the MTRR 66GG genotype did not increase NTD risk in children (OR 0.96, 95% CI 0.46-2.01). These data show that the MTRR 66GG genotype is a maternal risk factor for spina bifida especially when intracellular vitamin B12 status is low.
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Authors | Ivon J M van der Linden, Martin den Heijer, Lydia A Afman, Henkjan Gellekink, Sita H H M Vermeulen, Leo A J Kluijtmans, Henk J Blom |
Journal | Journal of molecular medicine (Berlin, Germany)
(J Mol Med (Berl))
Vol. 84
Issue 12
Pg. 1047-54
(Dec 2006)
ISSN: 0946-2716 [Print] Germany |
PMID | 17024475
(Publication Type: Comparative Study, Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't)
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Chemical References |
- Methylmalonic Acid
- methionine synthase reductase
- Ferredoxin-NADP Reductase
- Methylenetetrahydrofolate Reductase (NADPH2)
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Topics |
- Adolescent
- Adult
- Aged
- Alleles
- Case-Control Studies
- Child
- Child, Preschool
- Confidence Intervals
- Female
- Ferredoxin-NADP Reductase
(genetics)
- Humans
- Male
- Methylenetetrahydrofolate Reductase (NADPH2)
(genetics)
- Methylmalonic Acid
(blood)
- Middle Aged
- Mothers
- Odds Ratio
- Polymorphism, Genetic
- Risk Factors
- Spinal Dysraphism
(genetics, metabolism)
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