ab2002

IL-6 promoter polymorphism at position -174 modulates the phenotypic expression of polymyalgia rheumatica in biopsy-proven giant cell arteritis

M.A. Gonzalez-Gay¹, A.H. Hajeer², A. Dababneh², C. Garcia-Porrua¹, D.L. Mattey³, M.M. Amoli², W. Thomson², W.E.R. Ollier²

¹Division of Rheumatology, Hospital Xeral-Calde, Lugo, Spain; ²ARC Epidemiology Unit, Manchester University Medical School, Manchester; ³Staffordshire Rheumatology Centre, Stoke-on-Trent, United Kingdom.

ABSTRACT
Objectives
Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are related diseases in which diverse genetic and environmental factors are implicated. Both GCA and PMR are characterized by an intense acute phase reaction. In these syndromes the increased production of IL-6 has been observed. To investigate further the genetic influence of IL-6 in GCA and PMR we have examined the IL-6 promoter polymorphism (G to C) at position -174 in the 5' region in a series of patients from Northwest Spain diagnosed with GCA and/or PMR.

Methods
Sixty-two biopsy-proven GCA patients (30 of them with associated PMR) and 84 patients with isolated PMR were studied. Patients and ethnically matched controls (n = 124) were from the Lugo region (Galicia, Northwest Spain). Patients and controls were genotyped for HLA-DRB1 and IL-6 polymorphism at position -174 by molecular methods.

Results
IL-6-174 allele C was marginally increased in frequency in GCA patients with PMR manifestations compared with isolated GCA (pcorr: 0.06; OR = 2.3). The increase in the frequency of the CC genotype in GCA patients with PMR versus those with isolated GCA was statistically significant (p_corr: 0.02). The increased frequency of allele C in GCA patients with PMR was more commonly observed in HLA-DRB1*04 negative patients. However, this polymorphism was not associated with a higher risk of ischemic events in GCA or with relapses in PMR.

Conclusion
Allele C at position -174 in the 5' promoter region of the IL-6 gene may be associated with PMR in biopsy-proven GCA patients not carrying HLA-DRB1*04 alleles.

Key words
Giant cell arteritis, polymyalgia rheumatica, HLA-DRB1*04, IL-6 polymorphism.

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