title: Interleukin-18 promoter polymorphisms in Japanese patients with rheumatoid arthritis: protective effect of the T allele and T/T genotype at rs360722.
abstract: Rheumatoid arthritis (RA) is a chronic inflammatory disease with a strong genetic contribution to its pathogenesis. Among numerous candidate genes, cytokine gene polymorphisms have been implicated. Interleukin-18 (IL-18) induces production of tumor necrosis factor-α and promotes T helper (Th)1-type immune responses. This study investigates the association between IL-18 promoter polymorphisms and RA susceptibility. A total of 2471 Japanese case-control samples (1493 RA patients and 978 healthy controls) were examined. Three haplotype tag single-nucleotide polymorphisms, rs1946518A/C, rs360718T/G, and rs360722T/C, spanning from the 5'UTR to intron 1 were genotyped using allelic discrimination with the use of specific TaqMan probes, and three haplotypes (A-T-T, C-T-C, and A-G-C) were determined. Among these polymorphisms, the frequency of the T allele at rs360722, which tags the A-T-T haplotype, was significantly lower in the RA patient group compared with the normal subjects [0.46 versus 0.49, P = 0.0061, Fisher's exact probability test, odds ratio (OR) = 0.85, 95% confidence interval (CI) = 0.75-0.95]. Having the T/T genotype further increased the significance (0.20 versus 0.27, P = 0.0006, OR = 0.72, 95% CI = 0.58-0.86). Therefore, presence of the T allele and T/T genotype at rs360722 reduces the susceptibility of Japanese people to RA.
authors.affiliation: Institute of Rheumatology, Tokyo Women's Medical University School of Medicine, 10-22 Kawada-cho, Shinjuku-ku, Tokyo, 162-0054, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Sugiura
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kawaguchi
authors.forename: Katsunori
authors.initials: K
authors.lastname: Ikari
authors.forename: Hisae
authors.initials: H
authors.lastname: Ichida
authors.forename: Manabu
authors.initials: M
authors.lastname: Kawamoto
authors.forename: Shigeki
authors.initials: S
authors.lastname: Momohara
authors.forename: Masako
authors.initials: M
authors.lastname: Hara
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yamanaka
mesh_terms: D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
chemical_list: D020382:Interleukin-18