Interleukin-18 gene (IL18) promoter polymorphisms in patients with rheumatoid arthritis.

OBJECTIVE

Rheumatoid arthritis (RA) is a complex autoimmune disease with a strong genetic contribution to its pathogenesis. Proinflammatory cytokines play an important role in the inflammatory process in RA patients. The synthesis of cytokines is genetically determined. Cytokine gene polymorphisms have been implicated in a number of diseases, including RA. Interleukin-18 (IL-18) is a proinflammatory cytokine involved in the pathogenesis of RA. There are, however, controversial reports that the IL18 promoter polymorphism may be an independent marker of RA susceptibility. The aim of the present study was to examine the IL18 promoter polymorphism in patients with RA in association with disease susceptibility and activity.

METHODS

We examined 404 patients with RA diagnosed according to the criteria of the American College of Rheumatology (ACR). Allele-specific polymerase chain reaction (PCR) and PCR restriction fragment length polymorphism (RFLP) methods were used to analyse the single-nucleotide polymorphisms (SNPs) rs1946518, rs187238, rs360718, rs360722, rs360721, rs549908, and rs5744292 in the promoter region of the IL18 gene.

RESULTS

There were no significant differences in the distributions of the genotypes and haplotypes between RA patients and a control group. Age at RA diagnosis was lower in carriers of the rs1946518 CC and rs187238 GG genotypes. Erosive disease was diagnosed more frequently in patients with the rs1946518 CC and AC genotypes than in AA homozygotes.

CONCLUSION

These results show that these polymorphisms in the IL18 gene are associated only with some disease parameters and are generally not factors significantly influencing the course of RA.