한국인 성인형 스틸병 환자에서 Interleukin-18 유전자 다형성

Abstract

Objective: It has been suggested that overproduction of interleukin -18 (IL-18) may contributeto the pathogenesis of adult onset Still's disease (AOSD). Recently, positive association betweena polymorphism in the IL-18 gene and different diseases like diabetes, sarcoidosis and asthma hasbeen reported. The aim of the present study was to investigate the potential association of twosingle-nucleotide polymorphisms (SNPs) at position -137 (G/C) and -607 (C/A) in the promoterregion of the IL-18 gene with susceptibility and clinical feature of AOSD in the Korean population. Methods: We examined two SNPs of IL-18 in 70 patients with AOSD and 204 healthy controlindividuals. The genotyping were performed using sequence specific PCR. Haplotypes wereanalyzed by the estimated haplotype program. The patients with AOSD were subdivided into groups according to disease course: monocyclic systemic, polycyclic systemic, and chronicarticular type. Results: As for the -607 genotypes, 13 of the 69 patients had CC genotype (18.8%), 36 theCA type (52.2%) and 20 the AA type (29.0%). AOSD patients had higher frequency of A alleleat -607 when compared to controls (OR 1.48, 95% CI 1.00～2.18, p=0.048). AOSD patientshad significantly higher frequency of AA genotypes at -607 when compared to controls (AAvs CA& CC, OR 1.90, 95% CI 1.01～3.58, p=0.044). As for the -137 genotypes, of the 68patients, 57 had GG genotype (83.8%), 9 the GC type (13.2%) and 2 (2.9%) had the CC type. No differences were found in allele and genotype frequencies between two groups. Thehaplotype frequencies of the IL-18 polymorphism were not significantly different between patientswith AOSD and controls. The frequency of -137 GG genotype was significantly increased inchronic articular type compared to healthy control and systemic type of AOSD. Conclusion: In IL-18 gene polymorphisms, the A allele and AA genotye at position -607might be genetic risk factors for the development of AOSD in Korean population. Furtherinvestigation in larger groups is required to provide