Akhmad Makhmudi1, Ahmad Hamim Sadewa2, Teguh Aryandono3, Sumantra Chatterjee4, Hugo A Heij5. 1. a Pediatric Surgery Division, Department of Surgery, Faculty of Medicine , Universitas Gadjah Mada/Dr. Sardjito Hospital , Yogyakarta , Indonesia. 2. b Department of Biochemistry, Faculty of Medicine , Universitas Gadjah Mada , Yogyakarta , Indonesia. 3. c Oncologic Surgery Division, Department of Surgery, Faculty of Medicine , Universitas Gadjah Mada/Dr. Sardjito Hospital , Yogyakarta , Indonesia. 4. d Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine , Johns Hopkins University School of Medicine , Baltimore , MD , USA. 5. e Pediatric Surgery Division , Wilhelmina Kinderziekenhuis, UMC Utrecth , Netherlands.
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. PURPOSE: 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. MATERIAL AND 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.
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. PURPOSE: 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 gastroschisispatients. MATERIAL AND 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: Victor M Salinas-Torres; Rafael A Salinas-Torres; Ricardo M Cerda-Flores; Laura E Martínez-de-Villarreal Journal: Pediatr Surg Int Date: 2018-03-17 Impact factor: 1.827
Authors: Victor M Salinas-Torres; Rafael A Salinas-Torres; Ricardo M Cerda-Flores; Laura E Martínez-de-Villarreal Journal: Pediatr Surg Int Date: 2018-01-15 Impact factor: 1.827
Authors: Fiko Ryantono; Raman Sethi; Alvin Santoso Kalim; Priscillia Imelda; Devy Melati; Susan Simanjaya; William Widitjiarso; Ririd Tri Pitaka; Nur Arfian; Kristy Iskandar; Akhmad Makhmudi; Poh San Lai Journal: J Int Med Res Date: 2021-02 Impact factor: 1.671