Genetic Polymorphism in HIF1A and Oral Clefts

Objectives: Oral clefts are multifactorial conditions in which several distinct genetic and environmental factors have been identified. Studies with animal models demonstrated that hypoxia plays an important role in cleft etiology, however, the association between genetic variations in the Hypoxia-Inducible Factor-1 Alpha (HIF1A) gene and oral clefts in the human population has not yet been evaluated. Therefore, this study aimed to investigate the association between oral clefts and the genetic polymorphism rs2301113 in HIF1A.
Methods: One hundred and forty-eight oral cleft nuclear families were included in this study. Demographic data and data about mothers’ environmental condition during pregnancy were collected via a structured questionnaire of each patient. The association between the single nucleotide polymorphism rs2301113(A>C) in HIF1A was tested for oral cleft phenotypes (Cleft Lip with and without Palate-CL/P and Cleft Palate-CP) as a total group and as isolated phenotype. The genotyping was performed in real time PCR using Taqman assay. The transmission disequilibrium test (TDT) was used to check the distortion of the inheritance of alleles from parents to their affected offspring with an alpha of 5%.
Results: There was no under-transmitted polymorphism among affected progeny. There was no association between all cleft groups and polymorphism in HIF1A (p=0.622). The lack of association was also observed between CL/P group and polymorphism in HIF1A (p=0.555) and between CP group and polymorphism in HIF1A (p=0.818).
Conclusions: There was no association between the genetic polymorphism rs2301113 in HIF1A and oral clefts. Other genetic polymorphisms in this gene should be evaluated in order to elucidate if HIF1A plays a role in oral clefts etiology.