Vol.21 No.4

Original Article

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

Authors

Tomoko Sugiura1 , Yasushi Kawaguchi1 , Katsunori Ikari1 , Hisae Ichida1 , Manabu Kawamoto1 , Shigeki Momohara1 , Masako Hara1 , Hisashi Yamanaka1

  • Institute of Rheumatology, Tokyo Women’s Medical University School of Medicine, 10-22 Kawada-cho, Shinjuku-ku, Tokyo 162-0054, Japan
Received:

9 September 2010

Accepted:

29 November 2010

Published online:

12 January 2011

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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.

Key words

Interleukin-18 - Polymorphisms - Rheumatoid arthritis