Interleukin-18 promoter polymorphisms in Japanese patients with rheumatoid arthritis: protective effect of the T allele and T/T genotype at rs360722

• Published in: Modern rheumatology 2011-08, Vol.21 (4), p.359-364
• Main Authors: Sugiura, Tomoko, Kawaguchi, Yasushi, Ikari, Katsunori, Ichida, Hisae, Kawamoto, Manabu, Momohara, Shigeki, Hara, Masako, Yamanaka, Hisashi
• Format: Article
• Language: English
• Subjects: Alleles; Arthritis, Rheumatoid - genetics; Asian Continental Ancestry Group - genetics; Case-Control Studies; Female; Genetic Predisposition to Disease; Haplotypes; Humans; Interleukin-18; Interleukin-18 - genetics; Male; Polymorphism, Single Nucleotide; Polymorphisms; Promoter Regions, Genetic; Rheumatoid arthritis
• ISSN: 1439-7595; 1439-7609
• DOI: 10.3109/s10165-010-0399-y

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.