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).


CONCLUSIONS
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.
Chen
Der-Yuan
DY
Department of Internal Medicine, Taichung Veterans General Hospital, Taichung-Kang Road, Taichung City, 40705, Taiwan.
Chen
Yi-Ming
YM
Chen
Hsin-Hua
HH
Hsieh
Chia-Wei
CW
Lin
Chi-Chen
CC
Lan
Joung-Liang
JL
D000328:Adult; D016022:Case-Control Studies; D002681:China; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006801:Humans; D020382:Interleukin-18 / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D016706:Still's Disease, Adult-Onset / Q000175:diagnosis / Q000208:ethnology* / Q000235:genetics*
D020382:Interleukin-18