title: Association of folate metabolism genes MTHFR and MTRR with multiple complex congenital malformation risk in Chinese population of Shanxi.
abstract: Birth defects are common, serious malformations with a complex etiology that suggests involvement of both genetic and environmental factors. Low dietary folate and polymorphisms in genes of folate metabolism can influence risk for birth defects. In the present study 250 Chinese birth defects cases who suffered 1-8 types of birth defect disease phenotypes were subjected and two genetic variants in two folate metabolism key enzymes, rs1801394 of methionine synthase reductase (MTRR) and rs1801133 of methylenetetrahydrofolate reductase (MTHFR) were genotyped by using SNaPshot method. The results indicated that rs1801394 and rs1801133 were associated with multiple birth defects. According to homology of organogenesis, the disease phenotypes were classified into ectoderm-, mesoderm-, and endoderm-developed groups. Genetic analysis results displayed that as protective factors, genetic variants of rs1801133 and rs1801394 were associated with the risk of ectoderm-, and endoderm-developed malformations, but only the variant of rs1801394 was associated with the risk of mesoderm-developed malformations. Our present study first related nutrition metabolism related gene variants to germ layers and provided a novel understanding of an implication of earlier causation of birth defects pathogenesis in humans.
authors.affiliation: Beijing Municipal Key Laboratory of Child Development Nutrigenomics, Capital Institute of Pediatrics, Beijing 100020, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Beijing Municipal Key Laboratory of Child Development Nutrigenomics, Capital Institute of Pediatrics, Beijing 100020, China.
authors.forename: Baoling
authors.initials: B
authors.lastname: Bai
authors.affiliation: Beijing Municipal Key Laboratory of Child Development Nutrigenomics, Capital Institute of Pediatrics, Beijing 100020, China.
authors.forename: Xiaozhen
authors.initials: X
authors.lastname: Liu
authors.affiliation: Beijing Municipal Key Laboratory of Child Development Nutrigenomics, Capital Institute of Pediatrics, Beijing 100020, China.
authors.forename: Chunyue
authors.initials: C
authors.lastname: Miao
authors.affiliation: Beijing Municipal Key Laboratory of Child Development Nutrigenomics, Capital Institute of Pediatrics, Beijing 100020, China.
authors.forename: Huili
authors.initials: H
authors.lastname: Li
keywords: Birth defects; methionine synthase reductase (MTRR); methylenetetrahydrofolate reductase (MTHFR); multiple complex congenital malformation; single nucleotide olymorphism (SNP)
references.citation: Am J Hum Genet. 2008 Nov;83(5):572-81
references.pmid: 18976727
references.citation: Cell Metab. 2005 Mar;1(3):191-200
references.pmid: 16054062
references.citation: Hum Mol Genet. 2001 Mar 1;10(5):433-43
references.pmid: 11181567
references.citation: Am J Clin Nutr. 2010 May;91(5):1359-67
references.pmid: 20164316
references.citation: Thromb Res. 2014 Feb;133(2):229-34
references.pmid: 24315498
references.citation: Birth Defects Res A Clin Mol Teratol. 2007 Oct;79(10):702-7
references.pmid: 17729293
references.citation: Mol Genet Metab. 2008 Jul;94(3):336-42
references.pmid: 18413293
references.citation: PLoS One. 2009 Nov 16;4(11):e7844
references.pmid: 19924284
references.citation: J Nutr Biochem. 2011 Dec;22(12):1172-7
references.pmid: 21333513
references.citation: Biomed Rep. 2014 Mar;2(2):172-176
references.pmid: 24649091
references.citation: Clin Genet. 2009 May;75(5):409-23
references.pmid: 19459879
references.citation: Birth Defects Res A Clin Mol Teratol. 2010 Jul;88(7):575-81
references.pmid: 20641100
references.citation: Birth Defects Res A Clin Mol Teratol. 2011 Mar;91 Suppl 1:S44-50
references.pmid: 21384529
references.citation: J Nutr. 1952 Sep;48(1):61-79
references.pmid: 13000492
references.citation: Nat Genet. 1995 May;10(1):111-3
references.pmid: 7647779
references.citation: Development. 2010 Sep;137(18):3079-88
references.pmid: 20702562
references.citation: PLoS One. 2014 Mar 04;9(3):e89609
references.pmid: 24595101
references.citation: BMC Med Genet. 2009 Jun 03;10:49
references.pmid: 19493349
references.citation: J Nutr. 1956 Jan 10;58(1):125-34
references.pmid: 13286747
references.citation: Zhonghua Liu Xing Bing Xue Za Zhi. 2007 Jan;28(1):5-9
references.pmid: 17575922
references.citation: Am J Med Genet Suppl. 1987;3:29-42
references.pmid: 3130864
references.citation: Mol Genet Metab. 2007 May;91(1):85-97
references.pmid: 17369066
references.citation: BMC Med Genet. 2012 Aug 02;13:62
references.pmid: 22856873
references.citation: Biomed Environ Sci. 2009 Aug;22(4):340-4
references.pmid: 19950530
references.citation: Proc Natl Acad Sci U S A. 2009 Aug 25;106(34):14426-31
references.pmid: 19706528
references.citation: Biochemistry. 2004 Feb 24;43(7):1988-97
references.pmid: 14967039
references.citation: Birth Defects Res A Clin Mol Teratol. 2011 Jan;91(1):50-60
references.pmid: 21254359
references.citation: J Med Genet. 2004 Apr;41(4):256-60
references.pmid: 15060097
references.citation: Int J Dev Biol. 1999 May;43(3):183-205
references.pmid: 10410899
references.citation: Int J Womens Health. 2013;5:65-77
references.pmid: 23450007
references.citation: Am J Med Genet A. 2012 Oct;158A(10 ):2439-46
references.pmid: 22903727