Maternal genetic effects, exerted by genes involved in homocysteine remethylation, influence the risk of spina bifida.

Article Details

Citation

Doolin MT, Barbaux S, McDonnell M, Hoess K, Whitehead AS, Mitchell LE

Maternal genetic effects, exerted by genes involved in homocysteine remethylation, influence the risk of spina bifida.

Am J Hum Genet. 2002 Nov;71(5):1222-6. Epub 2002 Oct 9.

PubMed ID
12375236 [ View in PubMed
]
Abstract

There is currently considerable interest in the relationship between variation in genes that are involved in the folate-homocysteine metabolic axis and the risk of spina bifida. The evaluation of this relationship is, however, complicated by the potential involvement of both the maternal and the embryonic genotype in determination of disease risk. The present study was designed to address questions regarding both maternal and embryonic genetic risk factors for spina bifida by use of the two-step transmission/disequilibrium test. Analysis of data on variants of two genes involved in homocysteine remethylation/methionine biosynthesis--methionine synthase (MTR) A2756G and methionine synthase reductase (MTRR) A66G--provided evidence that both variants influence the risk of spina bifida via the maternal rather than the embryonic genotype. For both variants, the risk of having a child with spina bifida appears to increase with the number of high-risk alleles in the maternal genotype: MTR (R1=2.16, 95% CI 0.92-5.06; R2=6.58, 95% CI 0.87-49.67) and MTRR (R1=2.05, 95% CI 1.05-3.99; R2=3.15, 95% CI 0.92-10.85). These findings highlight the importance of considering both the maternal and embryonic genotype when evaluating putative spina bifida susceptibility loci.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Methionine synthaseQ99707Details
Methionine synthase reductaseQ9UBK8Details