title: Folate metabolism gene polymorphisms and risk for down syndrome offspring in Turkish women.
abstract: OBJECTIVE
  Down syndrome (DS) is the most common chromosomal abnormality. Many studies have assessed the association between maternal gene polymorphisms involved in folate metabolism and the risk of having a DS offspring, but data are conflicting. Six common polymorphisms in folate-metabolizing genes were analayzed to determine possible risk factors for a child to be born having DS (DS mothers); these samples were taken from 47 Turkish mothers having DS children (case group) and 49 control mothers. Investigated polymorphisms include methylenetetrahydrofolate reductase (MTHFR) C677T (rs1801133), A1298C (rs1801131), methionine synthase reductase (MTRR) A66G (rs1801394), methylenetetrahydrofolate dehydrogenase (MTHFD1) G1958A (rs2236225), reduced folate carrier (RFC1) A80G (rs1051266), and cystathionine β-synthase (CBS) 844ins68.
  
  
  RESULTS
  The frequency of the MTHFR 677C allele in DS mothers (79.8%) was significantly higher than in controls (66.3%), with a 0.499-fold increased risk of having a DS offspring (p=0.038 and 95% confidence interval [CI], 0.259-0.961). Mothers with the MTHFD1 1958A allele had a 1.880-fold increased risk of having a child with DS (p=0.031 and 95% CI, 1.060-3.335). No significant association was found for the other polymorphic variants in this study. Gene-gene interactions were not statistically significant.
  
  
  CONCLUSIONS
  Polymorphic variants of the enzymes involved in folate metabolism may play an important role in determining the susceptibility of having a DS offspring. The gene-nutrition, gene-gene interactions and ethnicity are important variables to be considered in future studies.
authors: 1 Department of Medical Biology and Genetics, Faculty of Medicine, Mersin University , Mersin, Turkey .
authors: Ozlem
authors: O
authors: Izci Ay
authors: Mustafa Ertan
authors: ME
authors: Ay
authors: Mehmet Emin
authors: ME
authors: Erdal
authors: Filiz
authors: F
authors: Cayan
authors: Sevinc
authors: S
authors: Tekin
authors: Fatma
authors: F
authors: Soylemez
authors: Mehmet Ali
authors: MA
authors: Sungur
authors: Didem
authors: D
authors: Derici Yıldırım
mesh_terms: D000328:Adult; D003541:Cystathionine beta-Synthase / Q000235:genetics / Q000378:metabolism; D004314:Down Syndrome / Q000235:genetics* / Q000378:metabolism; D004843:Epistasis, Genetic; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000235:genetics / Q000378:metabolism; D005492:Folic Acid / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP) / Q000235:genetics / Q000378:metabolism; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics / Q000378:metabolism; D015778:Minor Histocompatibility Antigens; D011110:Polymorphism, Genetic
chemical_list: D015778:Minor Histocompatibility Antigens; D005492:Folic Acid; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); C539735:MTHFD1 protein, human; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP); D003541:Cystathionine beta-Synthase