title: Polymorphisms in genes related to folate and cobalamin metabolism and the associations with complex birth defects.
abstract: OBJECTIVE
  To investigate the associations between biomarkers and genetic variants involved in homocysteine metabolism and the risk of complex birth defects.
  
  
  METHODS
  Total homocysteine (tHcy), folate, cobalamin, apo-transcobalamin (apo-TC) and apo-haptocorrin (apo-HC) were measured in the amniotic fluid of 82 women who were pregnant with a child having a complex birth defect, such as neural tube defect, cleft lip and/or palate, heart defect or omphalocele, and in 110 women pregnant with a non-malformed child. The determined genotypes of the child comprised of 5, 10-methylenetetrahydrofolate reductase (MTHFR 677C > T, 1298A > C), methionine synthase (MTR 2756A > G), methionine synthase reductase (MTRR 66A > G) and transcobalamin (TCN2 776C > G). Univariate and multivariate logistic regression analyses were performed.
  
  
  RESULTS
  Significantly lower cobalamin and higher apo-TC, apo-HC, tHcy and folate concentrations were determined in amniotic fluids of cases compared with controls (p< or =0.001). Logistic regression analysis revealed that after adjustment for maternal age, children carrying the MTHFR 677T allele showed a four-fold increased risk of having a complex birth defect, OR (95% CI) = 4.0 (1.1-15.4). Other genotypes did not show significant associations.
  
  
  CONCLUSIONS
  The MTHFR 677C > T polymorphism in conjunction with reduced folate- and/or cobalamin status may increase the risk of complex birth defects.
authors.affiliation: Department of Clinical Chemistry, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Brouns
authors.forename: N
authors.initials: N
authors.lastname: Ursem
authors.forename: J
authors.initials: J
authors.lastname: Lindemans
authors.forename: W
authors.initials: W
authors.lastname: Hop
authors.forename: S
authors.initials: S
authors.lastname: Pluijm
authors.forename: E
authors.initials: E
authors.lastname: Steegers
authors.forename: R
authors.initials: R
authors.lastname: Steegers-Theunissen
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics; D000328:Adult; D000653:Amniotic Fluid / Q000737:chemistry; D016022:Case-Control Studies; D002648:Child; D000013:Congenital Abnormalities / Q000235:genetics*; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000235:genetics; D005492:Folic Acid / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006710:Homocysteine / Q000235:genetics / Q000378:metabolism; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D011110:Polymorphism, Genetic; D011247:Pregnancy; D012307:Risk Factors; D014155:Transcobalamins / Q000032:analysis / Q000235:genetics; D014805:Vitamin B 12 / Q000032:analysis / Q000235:genetics* / Q000378:metabolism
chemical_list: D014155:Transcobalamins; D006710:Homocysteine; D005492:Folic Acid; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D014805:Vitamin B 12