An association study between hypoxia inducible factor-1alpha (HIF-1α) polymorphisms and osteonecrosis

• Published in: PloS one 2013-11, Vol.8 (11), p.e79647-e79647
• Main Authors: Chachami, Georgia, Kalousi, Alkmini, Papatheodorou, Loukia, Lyberopoulou, Aggeliki, Nasikas, Vasileios, Tanimoto, Keiji, Simos, George, Malizos, Konstantinos N, Georgatsou, Eleni
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Alcohol; Alleles; Arthritis; Biochemistry; Biocompatibility; Biomedical research; Blood flow; Bone blood flow; Bone marrow; Cancer; Cell Line; Diabetes; Exons - genetics; Female; Gene frequency; Genes; Genetic aspects; Health sciences; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit - genetics; Ischemia; Laboratories; Localization; Male; Medical research; Medicine; Middle Aged; Missense mutation; Mutation; NMR; Nuclear magnetic resonance; Osteonecrosis; Osteonecrosis - genetics; Pathogenesis; Patients; Polymerase chain reaction; Polymorphism, Restriction Fragment Length - genetics; Polymorphism, Single Nucleotide - genetics; Population; Population genetics; Prostate; Proteins; Restriction fragment length polymorphism; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Subgroups; Vascular endothelial growth factor; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0079647

Bone hypoxia resulting from impaired blood flow is the final pathway for the development of osteonecrosis (ON). The aim of this study was to evaluate if HIF-1α, the major transcription factor triggered by hypoxia, is genetically implicated in susceptibility to ON. For this we analyzed frequencies of three known HIF-1α polymorphisms: one in exon 2 (C111A) and two in exon 12 (C1772T and G1790A) and their association with ON in a Greek population. Genotype analysis was performed using PCR-RFLP and rare alleles were further confirmed with sequencing. We found that genotype and allele frequency of C1772T and G1790A SNP of HIF-1α (SNPs found in our cohort) were not significantly different in ON patients compared to control patients. Furthermore these SNPs could not be associated with the different subgroups of ON. At the protein level we observed that the corresponding mutations (P582S and A588T, respectively) are not significant for protein function since the activity, expression and localization of the mutant proteins is practically indistinguishable from wt in HEK293 and Saos-2 cells. These results suggest that these missense mutations in the HIF-1α gene are not important for the risk of developing ON.