Analysis of methionine synthase reductase polymorphisms for neural tube defects risk association.

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O'Leary VB, Mills JL, Pangilinan F, Kirke PN, Cox C, Conley M, Weiler A, Peng K, Shane B, Scott JM, Parle-McDermott A, Molloy AM, Brody LC

Analysis of methionine synthase reductase polymorphisms for neural tube defects risk association.

Mol Genet Metab. 2005 Jul;85(3):220-7. Epub 2005 Mar 17.

PubMed ID

15979034 [ View in PubMed

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Abstract

Methionine synthase reductase (MTRR) regenerates methylated cobalamin levels from the oxidised cob(II)alamin form and in so doing plays a crucial role in maintaining the active state of methionine synthase (MTR). MTR is an essential enzyme catalyzing the conversion of homocysteine to methionine. Single nucleotide polymorphisms (SNPs) within the MTRR gene may potentially compromise MTR activity leading to elevated homocysteine levels, a known risk factor for neural tube defects (NTDs). We studied the MTRR polymorphisms I22M (66A-->G), S175L (524C-->T), and K350R (1049A-->G) as potential NTD risk factors in a large homogeneous Irish NTD population. Degree of risk was assessed via case/control comparison, log-linear analysis, and transmission disequilibrium testing. No association was found between NTDs and I22M in mothers (p = 0.16, OR1.14 [0.95-1.38], n = 447) or cases (p = 0.13, OR1.15 [0.96-1.38], n = 470) compared to controls (n = 476). A dominant I22M paternal effect was found through case/control comparison and log-linear modelling (p = 0.019) (goodness-of-fit p=0.91, OR 1.46 [1.10-1.93], n = 423). No significant NTD association was found with S175L or K350R in cases or their parents and no interactions were observed between these polymorphisms and the D919G variant of MTR or the A222V variant of 5,10-methylenetetrahydrofolate reductase (MTHFR). We also compared the frequencies of I22M, S175L, and K350R in African-Americans versus American-Caucasians. The frequencies of I22M and K350R differed significantly between the two groups (p = 0.0005 and p = 0.0001, respectively). Our findings do not support an important role for these MTRR variants in NTDs.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Cyanocobalamin	Methionine synthase reductase	Protein	Humans	Unknown	Cofactor	Details

Polypeptides

Name	UniProt ID
Methionine synthase	Q99707	Details
Methionine synthase reductase	Q9UBK8	Details