title: An association study between hypoxia inducible factor-1alpha (HIF-1α) polymorphisms and osteonecrosis.
abstract: 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.
authors.affiliation: Laboratory of Biochemistry, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, Larissa, Greece ; Institute of Biomedical Research and Technology (BIOMED/CERETETH), Larissa, Greece.
authors.forename: Georgia
authors.initials: G
authors.lastname: Chachami
authors.forename: Alkmini
authors.initials: A
authors.lastname: Kalousi
authors.forename: Loukia
authors.initials: L
authors.lastname: Papatheodorou
authors.forename: Aggeliki
authors.initials: A
authors.lastname: Lyberopoulou
authors.forename: Vasileios
authors.initials: V
authors.lastname: Nasikas
authors.forename: Keiji
authors.initials: K
authors.lastname: Tanimoto
authors.forename: George
authors.initials: G
authors.lastname: Simos
authors.forename: Konstantinos N
authors.initials: KN
authors.lastname: Malizos
authors.forename: Eleni
authors.initials: E
authors.lastname: Georgatsou
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002460:Cell Line; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010020:Osteonecrosis / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D055815:Young Adult
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit