title: Effects of MTHFR c.677C>T, F2 c.20210G>A and F5 Leiden Polymorphisms in Gastroschisis.
abstract: BACKGROUND
  Gastroschisis is a developmental disorder involving the extrusion of fetal intestines through a defect in the abdominal wall. The mechanism is presumed to be a dual vascular/thrombotic pathogenesis, where normal right umbilical vein involution forms a possible site for thrombosis adjacent to the umbilical ring.
  
  
  OBJECTIVE
  The aim of this study was to demonstrate that the 3 common prothrombotic polymorphisms, MTHFR c.677C>T, F2 c.20210G>A, and F5 Leiden, were elevated in frequency in Indonesian gastroschisis patients.
  
  
  METHODS
  Three genetic markers were investigated in 46 patients with gastroschisis and 89 ethnicity-matched controls for association studies using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) or TaqMan Genotyping Assays on genomic DNA.
  
  
  RESULTS
  MTHFR c.677C>T showed a significant association with gastroschisis (OR = 2.1, 95% CI = 1.13-3.86; p = .018) but no affected infants had risk alleles for either F2 c.20210G>A or F5 Leiden. Further, the frequency of MTHFR risk allele (T) in patients with maternal age <25 years is marginally significant higher than those in cases with maternal age ≥25 years (p = .069) with an OR of 2.7 (95% CI = 0.90-8.07).
  
  
  CONCLUSIONS
  MTHFR is a common susceptibility factor for gastroschisis in Indonesia. The increased gastroschisis risk in offspring of younger maternal age suggests the thrombotic pathogenesis model. A founder effect is the most likely explanation for the rarity of the F2 and F5 Leiden polymorphisms in Indonesian population.
authors.affiliation: a Pediatric Surgery Division, Department of Surgery, Faculty of Medicine , Universitas Gadjah Mada/Dr. Sardjito Hospital , Yogyakarta , Indonesia.
authors.forename: Akhmad
authors.initials: A
authors.lastname: Makhmudi
authors.affiliation: b Department of Biochemistry, Faculty of Medicine , Universitas Gadjah Mada , Yogyakarta , Indonesia.
authors.forename: Ahmad Hamim
authors.initials: AH
authors.lastname: Sadewa
authors.affiliation: c Oncologic Surgery Division, Department of Surgery, Faculty of Medicine , Universitas Gadjah Mada/Dr. Sardjito Hospital , Yogyakarta , Indonesia.
authors.forename: Teguh
authors.initials: T
authors.lastname: Aryandono
authors.affiliation: d Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine , Johns Hopkins University School of Medicine , Baltimore , MD , USA.
authors.forename: Sumantra
authors.initials: S
authors.lastname: Chatterjee
authors.affiliation: e Pediatric Surgery Division , Wilhelmina Kinderziekenhuis, UMC Utrecth , Netherlands.
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Heij
authors.affiliation: a Pediatric Surgery Division, Department of Surgery, Faculty of Medicine , Universitas Gadjah Mada/Dr. Sardjito Hospital , Yogyakarta , Indonesia.|d Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine , Johns Hopkins University School of Medicine , Baltimore , MD , USA.
authors.lastname: Gunadi
mesh_terms: D000328:Adult; D000483:Alleles; D054458:Amplified Fragment Length Polymorphism Analysis; D005165:Factor V / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D020139:Gastroschisis / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007214:Indonesia; D007223:Infant; D008297:Male; D008423:Maternal Age; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011516:Prothrombin / Q000235:genetics*; D013923:Thromboembolism / Q000235:genetics*; D013927:Thrombosis / Q000235:genetics*
chemical_list: C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)
keywords: Gastroschisis; Indonesia; founder effect; maternal age; prothrombotic polymorphisms; vascular/thrombotic pathogenesis