Effects of MTHFR c.677C>T, F2 c.20210G>A and F5 Leiden Polymorphisms in Gastroschisis

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>Aor 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.