title: MTHFR C677T polymorphism and risk of congenital heart defects: evidence from 29 case-control and TDT studies.
abstract: BACKGROUND
  Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme for folate metabolism in humans; it is encoded by the MTHFR gene. Several studies have assessed the association between MTHFR C677T polymorphism and the risk of congenital heart defects (CHDs), while the results were inconsistent.
  
  
  RESULTS
  Multiple electronic databases were searched to identify relevant studies published up to July 22, 2012. Data from case-control and TDT studies were integrated in an allelic model using the Catmap and Metafor software. Twenty-nine publications were included in this meta-analysis. The overall meta-analysis showed significant association between MTHFR C677T polymorphism and CHDs risk in children with heterogeneity (P heterogeneity = 0.000) and publication bias (P egger = 0.039), but it turned into null after the trim-and-fill method was implemented (OR = 1.12, 95% CI = 0.95-1.31). Nevertheless, positive results were obtained after stratified by ethnicity and sample size in all subgroups except the mixed population. For mothers, there was significant association between the variant and CHDs without heterogeneity (P heterogeneity = 0.150, OR = 1.16, 95% CI = 1.05-1.29) and publication bias (P egger = 0.981). However, the results varied across each subgroup in the stratified analysis of ethnicity and sample size.
  
  
  CONCLUSIONS
  Both infant and maternal MTHFR C677T polymorphisms may contribute to the risk of CHDs.
authors.affiliation: Children's Hospital, Zhejiang University School of Medicine, Hangzhou, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Yujia
authors.initials: Y
authors.lastname: Wang
authors.forename: Fangqi
authors.initials: F
authors.lastname: Gong
authors.forename: Weihua
authors.initials: W
authors.lastname: Zhu
authors.forename: Songling
authors.initials: S
authors.lastname: Fu
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D006330:Heart Defects, Congenital / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D009035:Mothers; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012306:Risk
chemical_list: C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)
references.citation: Cardiovasc Ther. 2013 Aug;31(4):e27-33
references.pmid: 23865383
references.citation: Birth Defects Res A Clin Mol Teratol. 2008 Jun;82(6):474-81
references.pmid: 18452180
references.citation: Arch Med Res. 2007 Feb;38(2):212-8
references.pmid: 17227731
references.citation: Pediatr Cardiol. 2013 Jan;34(1):46-51
references.pmid: 22660520
references.citation: Zhonghua Yu Fang Yi Xue Za Zhi. 2009 Aug;43(8):700-4
references.pmid: 20021850
references.citation: Ann Hum Genet. 2012 Jan;76(1):9-16
references.pmid: 22175539
references.citation: Acta Obstet Gynecol Scand. 2005 Dec;84(12):1134-40
references.pmid: 16305696
references.citation: Nat Genet. 1995 May;10(1):111-3
references.pmid: 7647779
references.citation: N Engl J Med. 2006 Jul 13;355(2):206; author reply 209-11
references.pmid: 16848015
references.citation: Hum Mutat. 2000;15(3):280-7
references.pmid: 10679944
references.citation: Cochrane Database Syst Rev. 2009 Oct 07;(4):CD006612
references.pmid: 19821378
references.citation: Am J Obstet Gynecol. 2001 Apr;184(5):806-12; discussion 812-7
references.pmid: 11303187
references.citation: Birth Defects Res A Clin Mol Teratol. 2010 Feb;88(2):101-10
references.pmid: 19764075
references.citation: Clin Chem Lab Med. 2003 Mar;41(3):276-80
references.pmid: 12705333
references.citation: Eur J Pediatr. 1998 Jun;157(6):445-50
references.pmid: 9667396
references.citation: Am J Med Genet A. 2005 Sep 15;138(1):21-6
references.pmid: 16100725
references.citation: Cardiol Young. 2010 Jun;20(3):318-26
references.pmid: 20374669
references.citation: Prenat Diagn. 2007 Aug;27(8):704-8
references.pmid: 17510921
references.citation: Beijing Da Xue Xue Bao Yi Xue Ban. 2005 Feb 18;37(1):75-80
references.pmid: 15719048
references.citation: Am J Hum Genet. 1995 May;56(5):1052-9
references.pmid: 7726158
references.citation: Rev Port Cardiol. 2009 Jul-Aug;28(7-8):809-12
references.pmid: 19894660
references.citation: Cardiovasc Res. 2001 Aug 1;51(2):251-4
references.pmid: 11470464
references.citation: Int J Genet Mol Biol. 2010 Mar 1;2(3):43-47
references.pmid: 20657745
references.citation: Eur Heart J. 2006 Apr;27(8):981-7
references.pmid: 16524890
references.citation: Int J Cardiol. 2005 Oct 20;105(1):15-8
references.pmid: 16207540
references.citation: Circulation. 2010 Nov 30;122(22):2254-63
references.pmid: 21098447
references.citation: J Med Genet. 2006 Feb;43(2):162-6
references.pmid: 15951337
references.citation: Mol Hum Reprod. 2006 Jan;12(1):51-4
references.pmid: 16373366
references.citation: Birth Defects Res A Clin Mol Teratol. 2004 Oct;70(10):825-30
references.pmid: 15390319
references.citation: Ann Hum Genet. 2005 May;69(Pt 3):329-35
references.pmid: 15845037
references.citation: Am J Med. 2004 Jul 1;117(1):26-31
references.pmid: 15210385
references.citation: Obstet Gynecol. 2010 Aug;116(2 Pt 1):316-322
references.pmid: 20664391