Lack of association between hypoxia inducible factor-1 alpha gene polymorphisms and biopsy-proven giant cell arteritis

Clinical and Experimental Rheumatology

Miguel A. Gonzalez-Gay¹  Rogelio Palomino-Morales¹  Santos Castañeda¹  Jose L. Callejas-Rubio¹  Benjamin Fernadez-Gutierrez¹  Immaculada C. Morado¹  Orlando Torres¹  Encarnacion Amigo-Diaz¹  Jose A. Miranda-Filloy¹  Tomas R Vazquez-Rodriguez¹  Javier Martin¹  Carlos Gamallo¹ 

关键词: Giant cell arteritis;    disease susceptibility;    HIF-1α;    genetic studies;    gene polymorphism.;   

DOI  :  

学科分类：医学（综合）

来源: Pacini Editore SpA

【 摘 要 】

OBJECTIVES: 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. 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-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. CONCLUSIONS: Our results do not confirm an implication of HIF-1α gene polymorphisms in the susceptibility to and clinical expression of GCA.

【 授权许可】

Unknown