Folate and vitamin B12 metabolism in neural tube defects

Brody, Lawrence

Abstract

Research in the Molecular Pathogenesis is focused on defining changes in the genes that underlie inherited susceptibilities to common diseases such as cancer and birth defects. Changes in folate metabolism are correlated tumor formation and birth defects. Folate genes are also involved in the methylation of DNA. We are searching for genetic variants in genes related to folate, methionine and homocysteine metabolism. Individuals affected with cancer or spina bifida will be tested for these variants. Variants found at higher frequency in individuals with disease will help us identify genes associated with risk. More than 30 variants in folate related genes have been identified. A portion of these have been tested in spina bifida families. Initial evidence suggests that two of these new variants are associated with spina bifida risk. We will test the function consequences of these variants in experimental systems. The frequency of the same variants will be measured in individuals with cancer. If confirmed, these two genes will add to our understanding of neural tube defects and cancer risk.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Human Genome Research Institute (NHGRI)
• Type: Intramural Research (Z01)
• Project #: 1Z01HG000167-01
• Application #: 6430092
• Study Section: (GMBB)
• Support Year: 1
• Fiscal Year: 2000

Institution

• Name: Human Genome Research
• Country: United States

Publications

Molloy, Anne M; Brody, Lawrence C; Mills, James L et al. (2009) The search for genetic polymorphisms in the homocysteine/folate pathway that contribute to the etiology of human neural tube defects. Birth Defects Res A Clin Mol Teratol 85:285-94

Mills, James L; Molloy, Anne M; Parle-McDermott, Anne et al. (2008) Folate-related gene polymorphisms as risk factors for cleft lip and cleft palate. Birth Defects Res A Clin Mol Teratol 82:636-43

Molloy, Anne M; Kirke, Peadar N; Brody, Lawrence C et al. (2008) Effects of folate and vitamin B12 deficiencies during pregnancy on fetal, infant, and child development. Food Nutr Bull 29:S101-11;discussion S112-5

Parle-McDermott, Anne; Pangilinan, Faith; Mills, James L et al. (2007) The 19-bp deletion polymorphism in intron-1 of dihydrofolate reductase (DHFR) may decrease rather than increase risk for spina bifida in the Irish population. Am J Med Genet A 143A:1174-80

Lawrance, Andrea K; Deng, Liyuan; Brody, Lawrence C et al. (2007) Genetic and nutritional deficiencies in folate metabolism influence tumorigenicity in Apcmin/+ mice. J Nutr Biochem 18:305-12

Parle-McDermott, Anne; Mills, James L; Molloy, Anne M et al. (2006) The MTHFR 1298CC and 677TT genotypes have opposite associations with red cell folate levels. Mol Genet Metab 88:290-4

Parle-McDermott, Anne; Kirke, Peadar N; Mills, James L et al. (2006) Confirmation of the R653Q polymorphism of the trifunctional C1-synthase enzyme as a maternal risk for neural tube defects in the Irish population. Eur J Hum Genet 14:768-72

O'leary, Valerie B; Pangilinan, Faith; Cox, Christopher et al. (2006) Reduced folate carrier polymorphisms and neural tube defect risk. Mol Genet Metab 87:364-9

Parle-McDermott, Anne; Pangilinan, Faith; Mills, James L et al. (2005) A polymorphism in the MTHFD1 gene increases a mother's risk of having an unexplained second trimester pregnancy loss. Mol Hum Reprod 11:477-80

Swanson, Deborah A; Pangilinan, Faith; Mills, James L et al. (2005) Evaluation of transcobalamin II polymorphisms as neural tube defect risk factors in an Irish population. Birth Defects Res A Clin Mol Teratol 73:239-44