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

Valerie B. O'Leary, James L. Mills, Faith Pangilinan, Peadar N. Kirke, Christopher Cox, Mary Conley, Andrea Weiler, Kun Peng, Barry Shane, John M. Scott, Anne Parle-McDermott, Anne M. Molloy, Lawrence C. Brody

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)220-227
Number of pages8
JournalMolecular Genetics and Metabolism
Volume85
Issue number3
DOIs
StatePublished - Jul 2005
Externally publishedYes

Fingerprint

Neural Tube Defects
Polymorphism
Defects
Homocysteine
5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase
Methylenetetrahydrofolate Reductase (NADPH2)
Vitamin B 12
African Americans
Methionine
Single Nucleotide Polymorphism
methionine synthase reductase
Nucleotides
Genes
Parents
Mothers
Testing
Enzymes
Population

Keywords

  • Folate
  • Homocysteine
  • MTHFR
  • MTR
  • MTRR
  • Neural tube defects
  • Polymorphism
  • Spina bifida

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Endocrinology, Diabetes and Metabolism

Cite this

Analysis of methionine synthase reductase polymorphisms for neural tube defects risk association. / O'Leary, Valerie B.; Mills, James L.; Pangilinan, Faith; Kirke, Peadar N.; Cox, Christopher; Conley, Mary; Weiler, Andrea; Peng, Kun; Shane, Barry; Scott, John M.; Parle-McDermott, Anne; Molloy, Anne M.; Brody, Lawrence C.

In: Molecular Genetics and Metabolism, Vol. 85, No. 3, 07.2005, p. 220-227.

Research output: Contribution to journalArticle

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 2005, 'Analysis of methionine synthase reductase polymorphisms for neural tube defects risk association', Molecular Genetics and Metabolism, vol. 85, no. 3, pp. 220-227. https://doi.org/10.1016/j.ymgme.2005.02.003
O'Leary, Valerie B. ; Mills, James L. ; Pangilinan, Faith ; Kirke, Peadar N. ; Cox, Christopher ; Conley, Mary ; Weiler, Andrea ; Peng, Kun ; Shane, Barry ; Scott, John M. ; Parle-McDermott, Anne ; Molloy, Anne M. ; Brody, Lawrence C. / Analysis of methionine synthase reductase polymorphisms for neural tube defects risk association. In: Molecular Genetics and Metabolism. 2005 ; Vol. 85, No. 3. pp. 220-227.
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AU - Cox, Christopher

AU - Conley, Mary

AU - Weiler, Andrea

AU - Peng, Kun

AU - Shane, Barry

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