title: Lack of association between hypoxia inducible factor-1 alpha gene polymorphisms and biopsy-proven giant cell arteritis.
abstract: OBJECTIVE
  Since the transcription factor hypoxia-inducible factor 1 (HIF-1) is a key early mediator of the response to ischemia and giant cell arteritis (GCA) is a polygenic disease leading to severe ischemic complications, in the present study we analysed for first time the implication of two HIF-1alpha gene polymorphisms in the susceptibility to and clinical expression of GCA.
  
  
  METHODS
  Two hundred and fifteen biopsy-proven GCA patients and 470 matched controls were assessed. DNA from patients and controls was obtained from peripheral blood. Samples were genotyped for two single nucleotide polymorphisms, rs11549465 (C/T) and rs11549467 (G/A), using a pre-designed TaqMan allele discrimination assay. Post PCR, the genotype of each sample was attributed automatically by measuring the allelic specific fluorescence on the ABI PRIM 7900 sequence.
  
  
  RESULTS
  The HIF-1alpha, rs11549465 TT genotype was extremely uncommon in both GCA patients (2.3%) and controls (2.1%). Although the frequency of individuals carrying the CT or TT genotypes was increased in GCA patients (25.1%) compared to controls (20.4%) the difference was not statistically significant (OR 1.30 [95% CI: 0.89- 1.91]; p=0.17). Also, all GCA patients and most controls (98.9%) were homozygous for the rs11549467 GG genotype. GCA patients carrying the rs11549465 CT or TT genotypes had a slight increased risk of developing visual ischemic complications (33.1%) compared to the remaining GCA patients (22.8%); OR 1.60 (95% CI: 0.81- 3.16); p=0.18.
  
  
  CONCLUSIONS
  Our results do not confirm an implication of HIF-1alpha gene polymorphisms in the susceptibility to and clinical expression of GCA.
authors.affiliation: Instituto de Parasitología y Biomedicina López Neyra, Consejo Superior de Investigaciones Cientificas (CSIC), Granada, Spain.
authors.forename: Orlando
authors.initials: O
authors.lastname: Torres
authors.forename: Rogelio
authors.initials: R
authors.lastname: Palomino-Morales
authors.forename: Tomas R
authors.initials: TR
authors.lastname: Vazquez-Rodriguez
authors.forename: Carlos
authors.initials: C
authors.lastname: Gamallo
authors.forename: Immaculada C
authors.initials: IC
authors.lastname: Morado
authors.forename: Jose A
authors.initials: JA
authors.lastname: Miranda-Filloy
authors.forename: Encarnacion
authors.initials: E
authors.lastname: Amigo-Diaz
authors.forename: Jose L
authors.initials: JL
authors.lastname: Callejas-Rubio
authors.forename: Benjamin
authors.initials: B
authors.lastname: Fernadez-Gutierrez
authors.forename: Santos
authors.initials: S
authors.lastname: Castañeda
authors.forename: Immaculada C
authors.initials: IC
authors.lastname: Morado
authors.forename: Javier
authors.initials: J
authors.lastname: Martin
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Gonzalez-Gay
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D014644:Genetic Variation; D005838:Genotype; D013700:Giant Cell Arteritis / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit