Functional association of interleukin 18 gene -607 (C/A) promoter polymorphisms with disease course in Chinese patients with adult-onset Still's disease.

OBJECTIVE: Interleukin 18 (IL-18) has a central role in the pathogenesis of adult-onset Still's disease (AOSD). We investigated the functional association of -607 (C/A) IL-18 promoter polymorphisms with disease course in Chinese patients with AOSD.

METHODS: Sequence-specific primer polymerase chain reaction and the restriction fragment-length polymorphism method were used to analyze the genotypes of IL-18 promoter polymorphism at position -607 in 96 unrelated patients with AOSD and 164 ethnically-matched healthy controls. Serum IL-18 levels were determined using ELISA in patients with active untreated AOSD.

RESULTS: Significantly lower frequencies of single-nucleotide polymorphism -607/AA were observed in patients with AOSD compared to healthy controls (18.8% vs 31.1%, respectively; p < 0.05). Median levels of serum IL-18 were significantly lower in AOSD patients with AA genotype compared to those with CA genotype or CC genotype (147.5 pg/ml vs 410.5 pg/ml or 262.4 pg/ml, respectively; both p < 0.05). Significantly lower IL-18 levels were demonstrated in AOSD patients with a monocyclic systemic course than in those with a polycyclic systemic course or a chronic articular course. The AA genotype was more frequently observed in patients with monocyclic systemic course, which had the best prognosis, than in those with the other 2 disease courses. In contrast, a lower frequency of the AA genotype than the CA or the CC genotype was observed in patients with chronic disabling arthritis (5.5% vs 25.0% or 19.2%, respectively).

CONCLUSION: The SNP -607/AA genotype with lower IL-18 levels might be a genetically protective factor for the occurrence of AOSD in the Chinese population, against progression of chronic disabling arthritis.