title: Association study of hypoxia inducible factor 1alpha (HIF1alpha) with osteonecrosis of femoral head in a Korean population.
abstract: 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 HIF1alpha, a key transcription factor in controlling hypoxia condition, on ONFH, we analyzed HIF1alpha polymorphism and its genetic association with ONFH.
  
  
  METHODS
  We directly sequenced the HIF1alpha 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 HIF1alpha was also significantly associated with idiopathic ONFH in men (P=0.017).
  
  
  CONCLUSIONS
  We found that HIF1alpha polymorphisms are associated with idiopathic ONFH in men. These results suggest that variations in HIF1alpha may play an important role in the pathogenesis and risk factor for ONFH.
authors.affiliation: Skeletal Disease Genome Research Center, Kyungpook National University Hospital, 44-2, Samduk, Jung-gu, Daegu 700-412, Republic of Korea.
authors.forename: J Min
authors.initials: JM
authors.lastname: Hong
authors.forename: T-H
authors.initials: TH
authors.lastname: Kim
authors.forename: S-C
authors.initials: SC
authors.lastname: Chae
authors.forename: K-H
authors.initials: KH
authors.lastname: Koo
authors.forename: Y Jong
authors.initials: YJ
authors.lastname: Lee
authors.forename: E Kyun
authors.initials: EK
authors.lastname: Park
authors.forename: J-Y
authors.initials: JY
authors.lastname: Choi
authors.forename: H-M
authors.initials: HM
authors.lastname: Ryoo
authors.forename: S-Y
authors.initials: SY
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005269:Femur / Q000473:pathology*; D005271:Femur Head Necrosis / Q000453:epidemiology / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D007723:Korea / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit