ZFIN ID: ZDB-PUB-180526-6
Assessing the association between hypoxia during craniofacial development and oral clefts
Küchler, E.C., Silva, L.A.D., Nelson-Filho, P., Sabóia, T.M., Rentschler, A.M., Granjeiro, J.M., Oliveira, D., Tannure, P.N., Silva, R.A.D., Antunes, L.S., Tsang, M., Vieira, A.R.
Date: 2018
Source: Journal of applied oral science : revista FOB   26: e20170234 (Journal)
Registered Authors: Tsang, Michael
Keywords: none
MeSH Terms:
  • Adolescent
  • Adult
  • Aged
  • Analysis of Variance
  • Animals
  • Child
  • Child, Preschool
  • Cleft Lip/embryology*
  • Cleft Lip/etiology*
  • Cleft Palate/embryology*
  • Cleft Palate/etiology*
  • Disease Models, Animal
  • Female
  • Fetal Hypoxia/complications*
  • Fetal Hypoxia/genetics
  • Genetic Association Studies
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit/genetics*
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Real-Time Polymerase Chain Reaction
  • Severity of Illness Index
  • Statistics, Nonparametric
  • Young Adult
  • Zebrafish
PubMed: 29791568 Full text @ J Appl Oral Sci
Objectives To evaluate the association between hypoxia during embryo development and oral clefts in an animal model, and to evaluate the association between polymorphisms in the HIF-1A gene with oral clefts in human families. Material and Methods The study with the animal model used zebrafish embryos at 8 hours post-fertilization submitted to 30% and 50% hypoxia for 24 hours. At 5 days post-fertilization, the larvae were fixed. The cartilage structures were stained to evaluate craniofacial phenotypes. The family-based association study included 148 Brazilian nuclear families with oral clefts. The association between the genetic polymorphisms rs2301113 and rs2057482 in HIF-1A with oral clefts was tested. We used real time PCR genotyping approach. ANOVA with Tukey's post-test was used to compare means. The transmission/disequilibrium test was used to analyze the distortion of the inheritance of alleles from parents to their affected offspring. Results For the hypoxic animal model, the anterior portion of the ethmoid plate presented a gap in the anterior edge, forming a cleft. The hypoxia level was associated with the severity of the phenotype (p<0.0001). For the families, there was no under-transmitted allele among the affected progeny (p>0.05). Conclusion Hypoxia is involved in the oral cleft etiology, however, polymorphisms in HIF-1A are not associated with oral clefts in humans.