Lack of association between hypoxia inducible factor-1 alpha gene polymorphisms and biopsy-proven giant cell arteritis
O. Torres, R. Palomino-Morales, T.R. Vazquez-Rodriguez, C. Gamallo, I.C. Morado, J.A. Miranda-Filloy, E. Amigo-Diaz, J.L. Callejas-Rubio, B. Fernandez-Gutierrez, S. Castañeda, I.C. Morado, J. Martin, M.A. Gonzalez-Gay
2010 Vol.28, N°1 ,Suppl.57
PI 0040, PF 0045
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PMID: 20412701 [PubMed]
Accepted : 19/01/2010
In Press: 22/04/2010
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-1α gene polymorphisms in the susceptibility to and clinical expression of GCA.
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.
The HIF-1α, 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.
Our results do not confirm an implication of HIF-1α gene polymorphisms in the susceptibility to and clinical expression of GCA.