Background Interleukin (IL)-15 is a proinflammatory cytokine that is overexpressed in rheumatoid arthritis (RA) patients. Overproduction of IL-15 is generally considered to induce T cell activation and proliferation, possibly contributing to the pathogenesis of RA. Recently, genetic variants in IL-15 were reported to be associated with progression of joint destruction in RA in a European multi-cohort study.1 Thus far, some variants among the genetic predisposition factors identified in past reports have been found to be limited to particular ethnic groups, revealing the presence of genetic heterogeneity in RA. We investigated these associations in Japanese RA patients.
Objectives The purpose of this study is to explore the association between genetic variants in IL-15 and progression of joint destruction in Japanese RA patients.
Methods We studied 865 RA patients of whom Sharp/van der Heijde scores (SHS) of the hands were available at a disease duration of 5 years. DNA samples of the subjects were obtained from the IORRA (Institute of Rheumatology Rheumatoid Arthritis cohort study) DNA collection. IORRA is a project of a large-scale observational RA cohort. All of the patients who donated DNA samples consented to participate in this study in accordance with the process approved by the Tokyo Women’s Medical University Genome Ethics Committee. All of the patients satisfied the American College of Rheumatology 1987 revised criteria for the classification of RA. Two of four single nucleotide polymorphisms (SNPs) reported by Knevel R, et al.1 were selected: rs6821171 and rs7667746. The other SNPs were not polymorphic in the Japanese population. We genotyped rs6821171 and rs1521761 in absolute linkage disequilibrium with rs7667746, r2 = 1 in the Japanese population. Genotyping of SNPs was performed using the TaqMan fluorogenic 5’ nuclease assay (Applied Biosystems, Tokyo, Japan). Univariate regression analyses was performed for radiographic progression during the first 5 years after onset of RA and calculated as SHS of hands at the 5-year disease duration. For all statistical analyses, SHS were log-transformed to obtain a normal distribution.
Results Univariate linear regression analyses showed that neither of the SNPs were associated with progression of joint destruction in Japanese RA patients.
Conclusions No association was found between genetic variants in IL-15 and progression of joint destruction in Japanese RA patients. These results indicate the presence of IL-15 genetic heterogeneity among different ethnic populations.
Knevel R, et al. Genetic variants in IL15 associate with progression of joint destruction in rheumatoid arthritis: a multicohort study. Ann Rheum Dis. 2012 Oct; 71(10): 1651-7.
Disclosure of Interest S. Yoshida: None Declared, K. Ikari Speakers bureau: Abbott Japan Co. Ltd., Astellas Pharma Inc., Eisai Co. Ltd., Eli Lilly Japan K.K., Janssen Pharmaceutical K.K. Japan, Mitsubishi Tanabe Pharma Corporation, Y. Toyama: None Declared, A. Taniguchi: None Declared, H. Yamanaka Grant/research support from: The IORRA cohort was supported by non-restricted research grants from following companies; Abbott Japan Co. Ltd., Asahikasei Kuraray Medical Co. Ltd., Asahikasei Pharma Corporation, Astellas Pharma Inc., AstraZeneca K.K., Bristol-Myers Squibb, Chugai Pharmaceutical Co. Ltd., Daiichi Fine Chemical Co. Ltd., Daiichi Sankyo Co. Ltd., Dainippon Sumitomo Pharma Co. Ltd., Dentsu, Sudler & Hennessey Inc., Eisai Co. Ltd., GlaxoSmithKline K.K., Hisamitsu Pharmaceutical Co. Inc., Janssen Pharmaceutical K.K. Japan, Tobacco Inc., Kaken Pharmaceutical Co. Ltd., Kissei Pharmaceutical Co. Ltd., Kowa Pharmaceutical Co. Ltd., Maruho Co. Ltd., Mitsubishi Chemical Medience Corporation, Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co. Ltd., MSD K.K., Mundipharma K.K., Nippon Chemiphar Co. Ltd., Nippon Shinyaku Co. Ltd., Novartis Pharma K.K., Otsuka Pharmaceutical Co. Ltd., Pfizer Japan Inc., Sanofi-Aventis K.K., Santen Pharmaceutical Co. Ltd., Sanwa Kagaku Kenkyusho Co. Ltd., Sekisui Medical Co. Ltd., Shionogi Co. Ltd., Taishotoyama Pharmaceutical Co. Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited, Torii Pharmaceutical Co. Ltd., UCB Japan Co. Ltd., ZERIA Pharmaceutical Co. Ltd., Speakers bureau: Abbott Japan Co. Ltd., AstraZeneca K.K., Bristol-Myers Squibb, Chugai Pharmaceutical Co. Ltd., Eisai Co. Ltd., Janssen Pharmaceutical K.K. Japan, Mitsubishi Tanabe Pharma Corporation, Pfizer Japan Inc., Takeda Pharmaceutical Co. Ltd., Teijin Pharma Limited, UCB Japan Co. Ltd., S. Momohara: None Declared