| dc.contributor.author | MOLLOY, ANNE | en |
| dc.contributor.author | SCOTT, JOHN | en |
| dc.date.accessioned | 2015-12-09T11:34:46Z | |
| dc.date.available | 2015-12-09T11:34:46Z | |
| dc.date.issued | 1999 | en |
| dc.date.submitted | 1999 | en |
| dc.identifier.citation | D. C. Shields, P. N. Kirke, J. L. Mills, D. Ramsbottom, A. M. Molloy, H. Burke, D. G. Weir, J. M. Scott and A. S. Whitehead, The "thermolabile" variant of methylenetetrahydrofolate reductase and neural tube defects: An evaluation of genetic risk and the relative importance of the genotypes of the embryo and the mother, American Journal of Human Genetics, 64, 4, 1999, 1045-1055 | en |
| dc.identifier.other | Y | en |
| dc.identifier.uri | http://hdl.handle.net/2262/75144 | |
| dc.description.abstract | Recent reports have implicated the "thermolabile" (T) variant of methylenetetrahydrofolate reductase (MTHFR) in the causation of folate-dependent neural tube defects (NTDs). We report herein the largest genetic study of NTD cases (n=271) and families (n=218) to date, establishing that, in Ireland, the "TT" genotype is found in 18.8% of cases versus 8.3% of controls (odds ratio 2.57; confidence interval [CI] 1.48-4.45; P=.0005). The maternal and paternal TT genotypes have intermediate frequencies of 13.8% and 11.9%, respectively, indicating that the predominant MTHFR-related genetic effect acts via the TT genotype of the developing embryo. Analysis of the 218 family triads of mother, father, and affected child with log-linear models supports this interpretation, providing significant evidence that the case TT genotype is associated with NTDs (P=.02) but no evidence of a maternal TT genotypic effect (P=. 83). The log-linear model predicted that the risk of NTDs conferred by the case TT genotype is 1.61 (CI 1.06-2.46), consistent with the paramount importance of the case TT genotype in determining risk. There is no compelling evidence for more than a modest additional risk conferred by a maternal TT genotype. These results favor a biological model of MTHFR-related NTD pathogenesis in which suboptimal maternal folate status imposes biochemical stress on the developing embryo, a stress it is ill-equipped to tolerate if it has a TT genotype. | en |
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| dc.format.extent | 1045-1055 | en |
| dc.relation.ispartofseries | American Journal of Human Genetics | en |
| dc.relation.ispartofseries | 64 | en |
| dc.relation.ispartofseries | 4 | en |
| dc.rights | Y | en |
| dc.subject | folate-dependent neural tube defects (NTDs) | en |
| dc.subject.lcsh | folate-dependent neural tube defects (NTDs) | en |
| dc.title | The "thermolabile" variant of methylenetetrahydrofolate reductase and neural tube defects: An evaluation of genetic risk and the relative importance of the genotypes of the embryo and the mother | en |
| dc.type | Journal Article | en |
| dc.type.supercollection | scholarly_publications | en |
| dc.type.supercollection | refereed_publications | en |
| dc.identifier.peoplefinderurl | http://people.tcd.ie/amolloy | en |
| dc.identifier.rssinternalid | 21065 | en |
| dc.identifier.doi | http://dx.doi.org/10.1086/302310 | en |
| dc.rights.ecaccessrights | openAccess | |
| dc.subject.TCDTheme | Genes & Society | en |
| dc.subject.TCDTheme | International Development | en |
| dc.identifier.rssuri | http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10090889 | en |
