Lack of association between IFNGR1 gene polymorphisms and biopsy-proven giant cell arteritis.

OBJECTIVES: Since IFN-gamma plays a pivotal role in the pathogenesis of giant cell arteritis (GCA), a polygenic primary systemic vasculitis involving elderly people from Western countries, in the present study we analysed for first time the implication of three IFN-gamma receptor (IFNGR) 1 gene variants in the susceptibility to and clinical expression of GCA. METHODS: Two hundred and sixteen biopsy-proven GCA patients and 460 matched controls were assessed. DNA from patients and controls was obtained from peripheral blood. Samples were genotyped for three single nucleotide polymorphisms (SNPs) rs1327474 (-611A/G), rs11914 (+189G7C) and rs7749390 (+95C/T) of the IFNGR1 gene 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 PRISM 7900 sequence. RESULTS: No significant differences in the genotype or allele distribution between GCA patients and controls for the three IFNGR1 gene variants were found. Furthermore, no significant differences in the genotype distribution were observed when GCA patients were stratified according to the presence of specific clinical features of the disease such as polymyalgia rheumatica or severe ischemic complications including visual ischemic manifestations. CONCLUSIONS: Our results do not show an implication of IFNGR1gene polymorphisms in the susceptibility to and clinical expression of GCA.

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

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-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.