Assessing the association between hypoxia during craniofacial development and oral clefts

• Autor(a) principal: Küchler, Erika Calvano
• Data de Publicação: 2022
• Outros Autores: Silva, Lea Assed da, Nelson-Filho, Paulo, Sabóia, Ticiana M., Rentschler, Angela M., Granjeiro, José Mauro, Oliveira, Driely, Tannure, Patricia N., Silva, Raquel Assed da, Antunes, Leonardo Santos, Tsang, Michael, Vieira, Alexandre R.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Journal of applied oral science (Online)
• Texto Completo: https://www.revistas.usp.br/jaos/article/view/201715
• topic: Gene; Genetic; Children

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.