title: The 19-bp deletion polymorphism of dihydrofolate reductase (DHFR) and nonsyndromic cleft lip with or without cleft palate: evidence for a protective role.
abstract: OBJECTIVE
  Nonsyndromic cleft lip with or without cleft palate (NS-CL/P) are among the most common congenital birth defects worldwide. Several lines of evidence point to the involvement of folate, as well as folate metabolizing enzymes in risk reduction of orofacial clefts. Dihydrofolate reductase (DHFR) enzyme participates in the metabolic cycle of folate and has a crucial role in DNA synthesis, a fundamental feature of gestation and development. A functional polymorphic 19-bp deletion within intron-1 of DHFR has been associated with the risk of common congenital malformations. The present study aimed to evaluate the possible association between DHFR 19-bp deletion polymorphism and susceptibility to NS-CL/P in an Iranian population.
  
  
  METHODS
  The current study recruited 100 NS-CL/P patients and 100 healthy controls. DHFR 19-bp deletion was determined using an allele specific-PCR method.
  
  
  RESULTS
  We observed the DHFR 19-bp homozygous deletion genotype (D/D) vs. homozygous wild genotype (WW) was more frequent in controls than in NS-CL/P patients (25% vs. 13%), being associated with a reduced risk of NS-CL/P in both codominant (OR=0.33, P=0.027) and recessive (OR=0.45, P=0.046) tested inheritance models. We also stratified the cleft patients and reanalyzed the data. The association trend for CL+CL/P group compared to the controls revealed that the DD genotype in both codominant (OR=0.30, P=0.032) and recessive models (OR=0.35, P=0.031) was associated with a reduced risk of CL+CL/P.
  
  
  CONCLUSIONS
  Our results for the first time suggested the DHFR 19-bp D/D genotype may confer a reduced risk of NS-CL/P and might act as a protective factor against NS-CL/P in the Iranian subjects.
authors.affiliation: School of Dentistry, Zahedan University of Medical Sciences, Zahedan, Iran.
authors.forename: Firoozeh
authors.initials: F
authors.lastname: Rafighdoost
authors.affiliation: School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Amir
authors.initials: A
authors.lastname: Rafighdoost
authors.affiliation: Department of Anatomy, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
authors.forename: Houshang
authors.initials: H
authors.lastname: Rafighdoost
authors.affiliation: School of Dentistry, Zahedan University of Medical Sciences, Zahedan, Iran.
authors.forename: Mohammad-Ayoob
authors.initials: MA
authors.lastname: Rigi-Ladez
authors.affiliation: Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Hashemi
authors.affiliation: Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
authors.forename: Ebrahim
authors.initials: E
authors.lastname: Eskandari-Nasab
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000002:abnormalities*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D056726:Genetic Association Studies; D006801:Humans; D007223:Infant; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012016:Reference Values; D018570:Risk Assessment; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*; D055815:Young Adult
chemical_list: D013762:Tetrahydrofolate Dehydrogenase