title: A known functional polymorphism (Ile120Val) of the human PCMT1 gene and risk of spina bifida.
abstract: Folate binding protein 1 (Folr1) knockout mice with low maternal folate concentrations have been shown to be excellent animal models for human folate-responsive neural tube defects (NTDs). Previous studies using the Folr1 knockout mice revealed that maternal folate supplementation up-regulates the expression of the PCMT1 gene in Folr1 nullizygous neural tube tissue during neural tube closure. PCMT1 encodes the protein repair enzyme l-isoaspartate (d-aspartate) O-methyltransferase (PIMT) that converts abnormal d-aspartyl and l-isoaspartyl residues to the normal l-aspartyl form. PIMT is known to protect certain neural cells from Bax-induced apoptosis. Pcmt1-deficient mice present with abnormal AdoMet/AdoHcy homeostasis. We hypothesized that a known functional polymorphism (Ile120Val) in the human PCMT1 gene is associated with an increased risk of folate-responsive human NTDs. A case-control study was conducted to investigate a possible association between this polymorphism and risk of spina bifida. Compared to the Ile/Ile and Ile/Val genotypes, the homozygous Val/Val genotype showed decreased risk for spina bifida (adjusted odds ratio=0.6, 95% confidence interval: 0.4-0.9). Our results showed that the Ile120Val polymorphism of PCMT1 gene is a genetic modifier for the risk of spina bifida. Val/Val genotype was associated with a reduction in risk for spina bifida.
authors.affiliation: Center for Environmental and Genetic Medicine, Institute of Biosciences and Technology, Texas A&M University System Health Science Center, Houston, TX 77030, USA.
authors.forename: Huiping
authors.initials: H
authors.lastname: Zhu
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Gary M
authors.initials: GM
authors.lastname: Shaw
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Lammer
authors.forename: Richard H
authors.initials: RH
authors.lastname: Finnell
mesh_terms: D000328:Adult; D002140:California / Q000453:epidemiology; D016022:Case-Control Studies; D015331:Cohort Studies; D019587:Dietary Supplements; D005492:Folic Acid / Q000627:therapeutic use; D020022:Genetic Predisposition to Disease; D006630:Hispanic or Latino; D006801:Humans; D007231:Infant, Newborn; D011110:Polymorphism, Genetic; D026601:Protein D-Aspartate-L-Isoaspartate Methyltransferase / Q000235:genetics*; D012306:Risk; D016135:Spinal Dysraphism / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics* / Q000517:prevention & control; D044465:White People
chemical_list: D005492:Folic Acid; C435725:PCMT1 protein, human; D026601:Protein D-Aspartate-L-Isoaspartate Methyltransferase