title: Are the betaine-homocysteine methyltransferase (BHMT and BHMT2) genes risk factors for spina bifida and orofacial clefts?
abstract: Abnormalities in folate and/or homocysteine metabolism may adversely influence embryonic development, leading to the birth of infants with a variety of congenital malformations, including neural tube defects (NTDs) and craniofacial abnormalities. Based upon suggestive evidence that periconceptional folic acid supplementation is effective in preventing a significant proportion of the aforementioned birth defects, genetic variation in the folate biosynthetic pathways may influence the infant's susceptibility to these birth defects. The goal of our study was to investigate sequence variations in the betaine-homocysteine methyltransferase (BHMT) and betaine-homocysteine methyltransferase (BHMT2) genes as modifiers of risk of spina bifida, cleft palate, and cleft lip and palate. The results of this study indicated that individuals homozygous for the single nucleotide polymorphism R239Q in BHMT did not have elevated risks for spina bifida. Genotype frequencies for the BHMT2 rs626105 polymorphism also did not reveal any elevated risks for spina bifida, and only a modest, imprecise elevation of risk for orofacial clefts. The results of these experiments suggest that variants of the BHMT/BHMT2 genes in infants do not substantially contribute to the risk of spina bifida or orofacial clefts in our study population.
authors.affiliation: Center for Environmental and Genetic Medicine, Institute of Biosciences and Technology, Texas A and M University System Health Science Center, Houston, Texas 77030, USA.
authors.forename: Huiping
authors.initials: H
authors.lastname: Zhu
authors.forename: Stacey
authors.initials: S
authors.lastname: Curry
authors.forename: Shu
authors.initials: S
authors.lastname: Wen
authors.forename: Ned J
authors.initials: NJ
authors.lastname: Wicker
authors.forename: Gary M
authors.initials: GM
authors.lastname: Shaw
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Lammer
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.forename: Toghrul
authors.initials: T
authors.lastname: Jafarov
authors.forename: Richard H
authors.initials: RH
authors.lastname: Finnell
mesh_terms: D050940:Betaine-Homocysteine S-Methyltransferase; D002971:Cleft Lip / Q000175:diagnosis / Q000235:genetics; D002972:Cleft Palate / Q000175:diagnosis / Q000235:genetics; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007527:Isoenzymes / Q000235:genetics; D015810:Linkage Disequilibrium; D008780:Methyltransferases / Q000235:genetics*; D009056:Mouth Abnormalities / Q000175:diagnosis / Q000235:genetics*; D015997:Neonatal Screening; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D016135:Spinal Dysraphism / Q000175:diagnosis / Q000235:genetics*
chemical_list: C494551:BHMT2 protein, human; D007527:Isoenzymes; D004247:DNA; D008780:Methyltransferases; C494548:BHMT protein, human; D050940:Betaine-Homocysteine S-Methyltransferase