Rheumatoid arthritis (RA) has a wide range of clinical expressions which probably reflects different genetic backgrounds. Intercellular adhesion molecule-1 (ICAM-1) plays an important role in the inflammatory synovial activity in RA. The aim of this study was to examine the potential associations of ICAM-1 gene polymorphisms with RA and its severity.
Seventy-eight seropositive Italian RA patients with erosive disease entered the study. Radiographs of hands and feet 5 years after the diagnosis were available for 68 patients and were evaluated for the number of eroded joints. We obtained an erosive score for each patient by counting the number of joints with at least one erosion. Patients in the upper part of the distribution over the median were considered as fast eroders (FE) and the others as slow eroders (SE). Patients' records were also evaluated for the presence of extra-articular features. 228 healthy subjects of the same ethnic origin were selected as a control group. All of the RA patients and controls were genotyped by polymerase chain reaction and allele-specific oligonucleotide techniques for ICAM-1 polymorphisms G/R at codon 241 (exon 4) and E/K at codon 469 (exon 6).
The carriage rate of allele R241 was significantly higher in RA patients than in healthy controls (12.8% versus 5.7%, p = 0.039; odds ratio: 2.4 [95% CI 1.02 to 5.79]). The allele frequencies and carriage rate of the E 469 gene did not differ significantly between RA patients and the control group. When we compared the control group with the patients with more or less severe disease (presence or absence of extra-articular features, SE and FE) we found that only the group of patients with the more favourable course maintained a significant difference in the carriage rate of R241 (16.7 vs 5.7%, p = 0.009 for patients without extra-articular features and 18.9 vs 5.7%, p = 0.004 for SE patients).
Our preliminary findings show that G/R 241 polymorphism of ICAM-1 is associated with RA, and that this confers a reduced risk of extra-articular manifestations and is associated with a slow rate of joint destruction.