Usefulness of Cytokine Gene Polymorphisms for the Therapeutic Choice in Japanese Patients with Rheumatoid Arthritis

Abstract

Saki Tsujimoto, Yoshio Ozaki, Tomoki Ito, Shosaku Nomura First Department of Internal Medicine, Kansai Medical University, Hirakata, Osaka, JapanCorrespondence: Shosaku NomuraFirst Department of Internal Medicine, Kansai Medical University, 2-3-1 Shin-Machi, Hirakata, Osaka 573-1191, JapanTel + 81 72 804 2754Fax + 81 72 804 2041Email [email protected]: Rheumatoid arthritis (RA) is characterized by systemic synovitis with bone erosion and joint cartilage degradation. Although the analysis of polymorphisms in cytokine-encoding genes is important or understanding the pathophysiology of RA and selecting appropriate treatment for it, few studies have examined such single-nucleotide polymorphisms (SNPs) specifically in Japanese patients. This study was established to investigate the associations between polymorphisms in cytokine-encoding genes, autoantibodies and therapeutic responses in Japanese RA patients.Methods: The subjects in this study consisted of 100 RA patients and 50 healthy controls. We extracted data on sex, age, disease duration, rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibody, and therapeutic responses, including to methotrexate (MTX) and biological disease-modifying antirheumatic drugs (DMARDs). Genomic DNA was isolated from peripheral blood, which was genotyped for IL-10, TNF-α, TGF-β1, and IFN-γ polymorphisms.Results: Regarding IL-10 (− 592 C/A and − 819 C/T), significant decreases in the frequencies of the IL-10 (− 592) CC genotype and (− 819) CC genotype were found in RA patients compared with the levels in controls. For IFN-γ (+874 T/A), a significant decrease in the frequency of the TT genotype was found in RA patients compared with that in controls. Regarding TGF-β1 (+869 T/C), patients with positivity for anti-CCP antibody had a significantly lower frequency of the CC genotype than those with negativity for it. Furthermore, the IL-10 (− 592) CC genotype and (− 819) CC genotype might be related to the biological DMARD-response.Conclusion: Our results suggest that the analysis of polymorphisms in cytokine-encoding genes may be useful when selecting treatment for Japanese RA patients.Keywords: RA, SNP, cytokine gene polymorphism, anti-CCP antibody, biological DMARD

Keywords

• ra
• snp
• cytokine gene polymorphism
• anti-ccp antibody
• biological dmard