title: PCMT1 gene polymorphisms, maternal folate metabolism, and neural tube defects: a case-control study in a population with relatively low folate intake.
abstract: The PCMT1 gene encodes the protein repair enzyme protein-L-isoaspartate (D-aspartate) O-methyltransferase, which is known to protect certain neural cells against Bax-induced apoptosis. Previous studies have produced inconsistent results regarding the effects of PCMT1 (rs4816 and rs4552) polymorphisms on neural tube defects (NTDs). Reduced maternal plasma folate levels and/or elevated homocysteine (Hcy) levels are considered to be risk factors for NTDs. In order to clarify the key factors contributing to the apparent discrepancy and investigate gene-environment interaction, we conducted a case-control study including 121 cases and 146 matched controls to investigate the association between the two PCMT1 polymorphisms in fetuses and the risk of NTDs in the Chinese population of Lvliang, which has low folate intake. Maternal plasma folate and Hcy levels were also measured, and the interaction between fetal PCMT1 gene status and maternal folate metabolites was assessed. Maternal plasma folate concentrations in the NTD group were lower than in controls (10.23 vs. 13.08 nmol/L, adjusted P = 0.059), and Hcy concentrations were significantly higher (14.46 vs. 11.65 μmol/L, adjusted P = 0.026). Fetuses carrying the rs4816 AG + GG genotype, combined with higher maternal plasma Hcy, had a 6.46-fold (95 % CI 1.15-36.46) increased risk of anencephaly. The results of this study imply that the fetal PCMT1 rs4816 polymorphism may play only a weak role in NTD formation and that gene-environment interactions might be more significant.
authors.affiliation: Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, 100020, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Jianhua
authors.initials: J
authors.lastname: Wang
authors.forename: Jin
authors.initials: J
authors.lastname: Guo
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Chen
authors.forename: Zhen
authors.initials: Z
authors.lastname: Guan
authors.forename: Huizhi
authors.initials: H
authors.lastname: Zhao
authors.forename: Hua
authors.initials: H
authors.lastname: Xie
authors.forename: Chi
authors.initials: C
authors.lastname: Liu
authors.forename: Yihua
authors.initials: Y
authors.lastname: Bao
authors.forename: Jizhen
authors.initials: J
authors.lastname: Zou
authors.forename: Bo
authors.initials: B
authors.lastname: Niu
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
references.citation: Birth Defects Res A Clin Mol Teratol. 2007 Oct;79(10):702-7
references.pmid: 17729293
references.citation: Epilepsia. 2003;44 Suppl 3:14-23
references.pmid: 12790882
references.citation: Biochem Biophys Res Commun. 2009 Apr 17;381(4):523-7
references.pmid: 19239903
references.citation: Arch Dis Child Fetal Neonatal Ed. 1998 May;78(3):F235
references.pmid: 9713045
references.citation: Am J Epidemiol. 2000 May 1;151(9):862-77
references.pmid: 10791559
references.citation: Mol Genet Metab. 2003 Mar;78(3):216-21
references.pmid: 12649067
references.citation: Gene. 1999 Nov 29;240(2):333-41
references.pmid: 10580153
references.citation: Am J Clin Nutr. 2010 May;91(5):1359-67
references.pmid: 20164316
references.citation: Public Health Nutr. 2009 May;12(5):680-6
references.pmid: 18547453
references.citation: Biochemistry. 2008 Oct 7;47(40):10757-64
references.pmid: 18795804
references.citation: J Nutr. 2002 Jun;132(6):1357-60
references.pmid: 12042458
references.citation: Lancet. 1992 May 2;339(8801):1122-3
references.pmid: 1349147
references.citation: Teratology. 1994 Feb;49(2):143-9
references.pmid: 8016745
references.citation: Birth Defects Res A Clin Mol Teratol. 2007 Mar;79(3):187-210
references.pmid: 17177317
references.citation: N Engl J Med. 2007 Jul 12;357(2):135-42
references.pmid: 17625125
references.citation: Proc Nutr Soc. 2006 May;65(2):204-15
references.pmid: 16672082
references.citation: N Engl J Med. 1976 Feb 12;294(7):365-9
references.pmid: 1107843
references.citation: FASEB J. 1993 Nov;7(14):1344-53
references.pmid: 7901104
references.citation: N Engl J Med. 1992 Dec 24;327(26):1832-5
references.pmid: 1307234
references.citation: Arch Biochem Biophys. 1997 Oct 15;346(2):277-86
references.pmid: 9343375
references.citation: Exp Biol Med (Maywood). 2001 Apr;226(4):243-70
references.pmid: 11368417
references.citation: Mol Genet Metab. 2006 Jan;87(1):66-70
references.pmid: 16256389
references.citation: Neurochem Res. 2004 Jun;29(6):1105-12
references.pmid: 15176467
references.citation: Proc Natl Acad Sci U S A. 1997 Jun 10;94(12):6132-7
references.pmid: 9177182
references.citation: Biomed Environ Sci. 2008 Feb;21(1):37-44
references.pmid: 18478977
references.citation: Gene. 2012 Sep 1;505(2):340-4
references.pmid: 22647835
references.citation: Exp Neurol. 2008 Aug;212(2):515-21
references.pmid: 18589417
references.citation: Environ Health Perspect. 2006 Oct;114(10):1547-52
references.pmid: 17035141
references.citation: Clin Genet. 2003 Nov;64(5):424-8
references.pmid: 14616766
references.citation: J Hepatol. 2007 Jun;46(6):1119-25
references.pmid: 17336420
references.citation: Birth Defects Res A Clin Mol Teratol. 2009 Jun;85(6):574-81
references.pmid: 19180649
references.citation: Bioinformatics. 2005 Jan 15;21(2):263-5
references.pmid: 15297300
references.citation: Protein Eng Des Sel. 2009 Dec;22(12):713-21
references.pmid: 19801578
references.citation: J Biol Chem. 2002 Aug 2;277(31):27856-63
references.pmid: 12023972
references.citation: Teratology. 2002;66 Suppl 1:S17-22
references.pmid: 12239739
references.citation: Proc Natl Acad Sci U S A. 1996 Dec 24;93(26):15227-32
references.pmid: 8986792
references.citation: Biochem Biophys Res Commun. 2008 Jun 20;371(1):22-7
references.pmid: 18381200
references.citation: Metabolism. 1994 Dec;43(12):1475-80
references.pmid: 7990699
references.citation: J Hum Genet. 1999;44(5):275-88
references.pmid: 10496068