Intercellular adhesion molecule 1 gene polymorphisms in polymyalgia rheumatica/giant cell arteritis: Association with disease risk and severity

Objective. Intercellular adhesion molecule 1 (ICAM-1) is widely distributed in shoulder synovial membrane of active polymyalgia rheumatica (PMR) and s trongly expressed in granulomatous inflammatory infiltrate of the temporal artery in giant cell arteritis (GCA). ICAM-1 genes may contribute to the in flammatory PMR/GCA processes. We examined potential associations of ICAM-1 gene polymorphisms with PMR/GCA susceptibility and severity. Methods. We enrolled 121 consecutive patients with "pure" PMR and 56 patien ts with biopsy positive GCA residings in Reggio Emilia, Italy. Among patien ts with PMR, 91 had a followup duration of at least one year. Selected as c ontrol subjects were 228 healthy blood donors, 75 patients with nonarteriti c central retinal artery occlusion, and 116 cataract surgery patients from the same geographic area. All PMR/GCA patients and controls were genotyped by polymerase chain reaction and allele-specific oligonucleotide techniques for ICAM-1 polymorphism at codon 241 (exon 4) and codon 469 (exon 6). Results. The frequency of R241 was significantly higher in PMR/GCA patients [p = 0.00001, odds ratio (OR) 5.0 (95% confidence intervals, CI 2.6-9.6) ] , in pure PMR patients [p = 0.00001, OR 5.0 (95% CI 2.5-10.0)], and in GCA patients [p = 0.00005; OR 5.0 (95% CI 2.2-11.5)] compared to the healthy co ntrols. The frequency of R241 was significantly higher in total PMR/GCA pat ients compared to patients with nonarteritic central retinal artery occlusi on [p = 0.0007; OR 5.3 (95% CI 1.8-15.5)] and cataract surgery patients [p = 0.0003; OR 4.1 (95% CI 1.8-9.0)]. The distribution of E/K 469 genotype wa s similar in PMR/GCA patients and in the 3 control groups. Cox proportional hazards modeling identified 2 variables that independently increased the r isk of PMR relapse/recurrence: erythrocyte sedimentation rate at diagnosis > 72 mm/h [relative risk 1.6 (95% CI 1.1-2.3)] and the presence of R241 all ele [relative risk 1.6 (95% CI 1.1-2.4)]. Conclusion. OUT findings show that G/R 241 polymorphism of ICAM-1 is associ ated with PMR/GCA susceptibility and confers an increased risk of relapse/r ecurrence in PMR.