s36_ab2

Interferon-gamma gene microsatellite polymorphisms in patients with biopsy-proven giant cell arteritis and isolated polymyalgia rheumatica

M.A. Gonzalez-Gay¹, A.H. Hajeer², A. Dababneh², C. Garcia-Porrua¹, M.M. Amoli², J. Llorca³, W.E.R. Ollier²

¹Division of Rheumatology, Hospital Xeral-Calde, Lugo, Spain; ²Centre for Integrated Genomic Medical Research, School of Epidemiology, and Health Sciences, University of Manchester, Manchester, United Kingdom; ³Department of Preventive Medicine and Public Health, University of Cantabria School of Medicine, Santander, Spain.

ABSTRACT
Objectives
Inflammatory cytokines are implicated in the pathogenesis of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR). In this study we have examined the potential association of a CA repeat polymorphism in the first intron of the interferon gamma (IFN-g) gene with disease susceptibility and clinical expression of these conditions.

Methods
Seventy-nine patients with isolated PMR, 59 biopsy-proven GCA patients and 129 ethnically matched controls from Lugo (NW Spain) were studied. Patients and controls were genotyped by molecular methods for the microsatellite dinucleotide (CA) repeat within the first intron of IFN-g gene.

Results
No significant differences in the distribution of alleles for the IFN-g gene polymorphism between GCA and isolated PMR patients and controls were found. However, the frequency of IFN-g allele *4 (128 bp) was reduced in GCA patients (33.1%) compared with isolated PMR patients (46.2%). Also, GCA patients with visual ischemic manifestations exhibited a significantly reduced frequency of IFN-g allele *4 compared with those without visual manifestations (17.9% versus 42.5%; p = 0.05 [OR: 0.36, 95% CI: 0.13 Ð1.00]). Moreover, allele *3 (126 bp) was over-represented in the GCA patients with visual ischemic manifestations (71.4% versus 44.4% in the remaining GCA patients; p =0.01 [OR = 3.13, 95% CI: 1.27-7.68]).

Conclusions
In GCA, INF-g functional polymorphisms are associated with clinical manifestations of severity rather than susceptibility to this vasculitis.

Key words
Giant cell arteritis, polymyalgia rheumatica, IFN-g gene.

Please address correspondence and reprint requests to: Miguel A. González-Gay, MD, PhD, Rheumatology Division, Hospital Xeral-Calde, c) Dr. Ochoa s/n, 27004, Lugo, Spain.
E-mail: miguelaggay@hotmail.com