Association study of hypoxia inducible factor 1α (HIF1α) with osteonecrosis of femoral head in a Korean population

Objective: Disruption of the vascular supply to the bone and subsequent hypoxia has been implicated in the pathogenesis of osteonecrosis (ON) of the femoral head (ONFH). To evaluate the genetic effect of HIF1α, a key transcription factor in controlling hypoxia condition, on ONFH, we analyzed HIF1α polymorphism and its genetic association with ONFH. Methods: We directly sequenced the HIF1α gene in 24 Korean individuals and identified four sequence variants. Four polymorphisms (-2755C>A, +41224T>C, +45319C>T, +51610C>T) were genotyped in ONFH (n = 384). ONFH patients were divided into three subgroups based on etiological factors: idiopathic (129 cases), steroid (59 cases) and alcohol (196 cases) ON groups. Results: We found that the allele frequency of -2755C>A and the genotype frequencies of +41224T>C and +51610C>T were significantly associated with idiopathic ONFH in men (P = 0.0409, 0.0113, 0.0269, respectively). In addition, haplotype (CTCC) of HIF1α was also significantly associated with idiopathic ONFH in men (P = 0.017). Conclusions: We found that HIF1α polymorphisms are associated with idiopathic ONFH in men. These results suggest that variations in HIF1α may play an important role in the pathogenesis and risk factor for ONFH.