title: Polymorphisms of 5,10-methylenetetrahydrofolate reductase and cystathionine beta-synthase genes as a risk factor for neural tube defects in Sétif, Algeria.
abstract: BACKGROUND
  Neural tube defects (NTD) are severe congenital malformations due to a failure in neural tube formation at the beginning of pregnancy. The etiology of NTD is multifactorial, with environmental and genetic determinants. We suggest a study of gene-gene interactions regarding the possible association of NTD with specific mutations of 5,10-methylenetetrahydrofolate reductase (MTHFR) and cystathionine beta-synthase (CBS) genes.
  
  
  METHODS
  The genetic analysis of the MTHFR C677T polymorphism was performed by real-time polymerase chain reaction (PCR) on a Light Cycler, the CBS genotype was analyzed by PCR in a thermal cycler. Ninety-two mothers who had conceived NTD children and 48 fathers were investigated. A group of 147 adults, including 82 apparently healthy women, was used as control.
  
  
  RESULTS
  Among control mothers, 35 (43%) were heterozygous for the C677T variant and 14 (17%) were TT homozygous. Among the cases, 25 (52%) out of 48 mothers and 22 (46%) out of 48 fathers carried the T allele; 9 mothers (19%) and 5 fathers (10%) had the TT genotype. A homozygous C677T mutation was not an NTD risk factor in this preliminary study in an Algerian population; a possible gene-gene interaction between the MTHFR C677T polymorphism and the CBS 844ins68 has also been examined in relation to NTD, but no such association has been shown. There was a statistically significant difference between the heterozygosity genotype frequency of CBS polymorphisms in mothers with a previous child with NTD compared with the mother controls (odds ratio: 3.72; 95% CI: 1.59-8.73).
  
  
  CONCLUSIONS
  Our results with Algerian NTD mothers did not show a significant association for any group, suggesting that the thermolabile variant C677T in the MTHFR gene is not a risk factor for a mother to have NTD offspring; rather, folic acid supplementation or fortification should become mandatory for all women of reproductive age in Algeria.
authors.affiliation: Department of Biology, Faculty of Sciences, University of Sétif, 19000 Sétif, Algeria. b.houcher@yahoo.fr
authors.forename: Bakhouche
authors.initials: B
authors.lastname: Houcher
authors.forename: Romyla
authors.initials: R
authors.lastname: Bourouba
authors.forename: Farida
authors.initials: F
authors.lastname: Djabi
authors.forename: Erkan
authors.initials: E
authors.lastname: Yilmaz
authors.forename: Yonca
authors.initials: Y
authors.lastname: Eğin
authors.forename: Nejat
authors.initials: N
authors.lastname: Akar
mesh_terms: D000328:Adult; D000462:Algeria / Q000453:epidemiology; D000483:Alleles; D016022:Case-Control Studies; D016001:Confidence Intervals; D003541:Cystathionine beta-Synthase / Q000235:genetics*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D009436:Neural Tube Defects / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011247:Pregnancy; D015995:Prevalence; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2); D003541:Cystathionine beta-Synthase