title: MTR, MTRR, and MTHFR Gene Polymorphisms and Susceptibility to Nonsyndromic Cleft Lip With or Without Cleft Palate.
abstract: OBJECTIVE
  To examine the associations of methionine synthase (MTR), methionine synthase reductase (MTRR), and methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms with the susceptibility to nonsyndromic cleft lip with or without cleft palate (NSCL/P).
  
  
  METHODS
  Between May 2012 and August 2014, 147 NSCL/P patients (case group) and 129 healthy volunteers (control group) were recruited for the study. The MTR A2756G, MTRR A66G, MTHFR C677T and MTHFR A1298C polymorphisms were assessed by polymerase chain reaction-restriction fragment length polymorphism. Haplotype analyses were performed with SHEsis software. Logistic regression analysis was used to evaluate the possible risk factors for NSCL/P. Generalized multifactor dimensionality reduction (GMDR) was applied to detect gene-gene interactions.
  
  
  RESULTS
  MTR A2756G, MTRR A66G, and MTHFR C677T gene polymorphisms were associated with the risk of NSCL/P (all p < 0.05). Logistic regression analysis revealed that MTR A2756G, MTR RA66G, and MTHFR C667T might increase the risk of NSCL/P (odds ratio [OR] = 0.270, 95% confidence interval [95% CI] = 0.106-0.689; OR = 0.159, 95% CI = 0.069-0.368; OR = 0.343, 95% CI = 0.139-0.844). The CA haplotype in the MTHFR gene may serve as a protective factor for NSCL/P (OR = 0.658, 95% CI = 0.470-0.923), and the TA haplotype might be a risk factor (OR = 2.001, 95% CI = 1.301-3.077). GMDR revealed that the optimal models were two- and four-dimensional models with prediction accuracies of 75.73% (p = 0.001) and 77.21% (p = 0.001) and the best cross-validation consistencies of 10/10 and 10/10, respectively.
  
  
  CONCLUSIONS
  MTR A2756G, MTRR A66G, and MTHFR C677T polymorphisms may be related to NSCL/P, and interactions were detected between the MTR A2756G, MTRR A66G, and MTHFR C677T and A1298C polymorphisms.
authors.affiliation: Department of Oral Maxillofacial Surgery, the First Affiliated Hospital, Harbin Medical University , Harbin, China .
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Oral Maxillofacial Surgery, the First Affiliated Hospital, Harbin Medical University , Harbin, China .
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Jiao
authors.affiliation: Department of Oral Maxillofacial Surgery, the First Affiliated Hospital, Harbin Medical University , Harbin, China .
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Wang
authors.affiliation: Department of Oral Maxillofacial Surgery, the First Affiliated Hospital, Harbin Medical University , Harbin, China .
authors.forename: Xiang-Yu
authors.initials: XY
authors.lastname: Sun
authors.affiliation: Department of Oral Maxillofacial Surgery, the First Affiliated Hospital, Harbin Medical University , Harbin, China .
authors.forename: Chen
authors.initials: C
authors.lastname: Dong
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002971:Cleft Lip / Q000201:enzymology / Q000235:genetics*; D002972:Cleft Palate / Q000201:enzymology / Q000235:genetics*; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000235:genetics* / Q000378:metabolism; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; C585801:MTR protein, human