title: Interleukin-18 promoter polymorphisms in patients with Behçet's disease.
abstract: Behçet's disease (BD) is an idiopathic systemic inflammatory disease and is considered to be a T helper 1 (Th1) type cytokine driven disorder. Moreover, levels of interleukin-18 (IL-18), a pivotal mediator of Th1 cytokine response, have been reported to be upregulated in BD. Therefore, we investigated the distribution of IL-18 promoter -607 C/A and -137 G/C polymorphisms in 103 BD patients (mean age 41.0 years; 48 male, 55 female) using allele-specific-polymerase chain reaction. As compared with healthy control subjects, BD patients had a significantly higher frequency of the -607 CC genotype (42.7% vs 23.3%, odds ratio [OR] = 2.455, 95% confidence interval [CI] = 1.350-4.461, p(c) = 0.021) and a higher frequency of the -607 C allele (60.7% vs 48.1%, OR = 1.668, 95% CI = 1.129-2.464, p = 0.0101). Haplotype analysis showed that BD patients had significantly less -607A/-137G haplotype (27.3% vs 44.2%, OR = 0.469, 95% CI = 0.268-0.820, p(c) = 0.032) and -607A/-137G haplotype homozygote (5.8% vs 20.4%, OR = 0.242, 95% CI = 0.096-0.612, p(c) = 0.014) than control subjects. In addition, the frequency of -607C/-137G haplotype homozygote was significantly higher in BD patients than control subjects (48.5% vs 20.4%, OR = 3.684, 95% CI = 1.997-6.791, p(c) = 0.0014). Although there were no associations between the polymorphisms and clinical manifestations or severity, patients with the -607 CC genotype or -607C/-137G haplotype homozygote showed significantly earlier symptom development (p = 0.034 by ANOVA; p = 0.009 by t-test, respectively) than those with other genotypes or diplotypes. These results suggest that the IL-18 promoter gene is a candidate susceptibility gene in BD patients.
authors.affiliation: Department of Internal Medicine, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Yun Jong
authors.initials: YJ
authors.lastname: Lee
authors.forename: Seong Wook
authors.initials: SW
authors.lastname: Kang
authors.forename: Jeong Jin
authors.initials: JJ
authors.lastname: Park
authors.forename: Young Deok
authors.initials: YD
authors.lastname: Bae
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Lee
authors.forename: Eun Bong
authors.initials: EB
authors.lastname: Lee
authors.forename: Yeong Wook
authors.initials: YW
authors.lastname: Song
mesh_terms: D000293:Adolescent; D000368:Aged; D001168:Arthritis / Q000209:etiology; D001528:Behcet Syndrome / Q000150:complications / Q000235:genetics* / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics* / Q000276:immunology; D007723:Korea; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014605:Uveitis / Q000209:etiology
chemical_list: D020382:Interleukin-18