title: Polymorphisms within the vitamin B12 dependent methylmalonyl-coA mutase are not risk factors for neural tube defects.
abstract: Methionine synthase and methylmalonyl-CoA mutase (mutase) are the only two known vitamin B(12) (B(12)) dependent enzymes in humans. A lower level of B(12) has been shown to be an independent maternal risk factor for neural tube defects (NTDs) prompting an investigation of common genetic variants within B(12) dependent enzymes. To investigate the role of methylmalonyl-CoA mutase variants we studied 279 complete NTD triads (NTD affected case and both parents) and 256 controls. Based on case-control and family based (transmission disequilibrium test) analyses we did not find an association between the mutase single nucleotide polymorphisms (SNPs) K212K (636A-->G), H532R (1595A-->G) and V671I (2011G-->A) and NTDs. However, there was a significant difference in the frequencies of these polymorphisms between a group of African Americans and American Caucasians (K212K, P=0.002; H532R, P</=0.001; V671I, P=0.006). In conclusion, common variants in the mutase gene do not appear to be risk factors for NTDs but their allele frequencies are significantly different between ethnic groups.
authors.affiliation: Department of Biochemistry, Trinity College Dublin, Dublin, Ireland.
authors.forename: Anne
authors.initials: A
authors.lastname: Parle-McDermott
authors.forename: Edward J
authors.initials: EJ
authors.lastname: McManus
authors.forename: James L
authors.initials: JL
authors.lastname: Mills
authors.forename: Valerie B
authors.initials: VB
authors.lastname: O'Leary
authors.forename: Faith
authors.initials: F
authors.lastname: Pangilinan
authors.forename: Christopher
authors.initials: C
authors.lastname: Cox
authors.forename: Andrea
authors.initials: A
authors.lastname: Weiler
authors.forename: Anne M
authors.initials: AM
authors.lastname: Molloy
authors.forename: Mary
authors.initials: M
authors.lastname: Conley
authors.forename: Deborah
authors.initials: D
authors.lastname: Watson
authors.forename: John M
authors.initials: JM
authors.lastname: Scott
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Brody
authors.forename: Peadar N
authors.initials: PN
authors.lastname: Kirke
mesh_terms: D016022:Case-Control Studies; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D016014:Linear Models; D015810:Linkage Disequilibrium; D008297:Male; D008765:Methylmalonyl-CoA Mutase / Q000235:genetics* / Q000378:metabolism; D009436:Neural Tube Defects / Q000235:genetics*; D010375:Pedigree; D011110:Polymorphism, Genetic; D044469:Racial Groups / Q000235:genetics; D012307:Risk Factors; D014805:Vitamin B 12 / Q000378:metabolism*
chemical_list: D008765:Methylmalonyl-CoA Mutase; D014805:Vitamin B 12