Usefulness of Cytokine Gene Polymorphisms for the Therapeutic Choice in Japanese Patients with Rheumatoid Arthritis.
Usefulness of Cytokine Gene Polymorphisms for the Therapeutic Choice in Japanese Patients with Rheumatoid Arthritis.
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DOI：
10.2147/ijgm.s287505
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发表时间：
2021
影响因子：
2.3
通讯作者：
Nomura S
中科院分区：
文献类型：
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作者：
Tsujimoto S;Ozaki Y;Ito T;Nomura S
类风湿关节炎(RA)以全身性滑膜炎为主，伴有骨质侵蚀和关节软骨退化。尽管分析细胞因子编码基因的多态性对于了解RA的病理生理机制和选择合适的治疗方法很重要，但很少有研究专门研究这种单核苷酸多态(SNPs)在日本患者中的表现。本研究旨在探讨日本类风湿关节炎患者细胞因子编码基因、自身抗体和治疗反应之间的关系。研究对象包括100例类风湿关节炎患者和50例健康对照。我们提取了关于性别、年龄、病程、类风湿因子(RF)、抗环瓜氨酸肽(抗CCP)抗体以及对甲氨蝶呤(MTX)和生物抗风湿药物(DMARDS)的治疗反应的数据。提取外周血基因组DNA，进行IL-10、肿瘤坏死因子-α、转化生长因子-β-1和干扰素-γ的基因分型。在IL-10(−592C/A和−819C/T)方面，RA患者IL-10(−592CC)和(−819)CC的频率明显低于对照组。干扰素-γ(+874T/A)基因TT型频率在类风湿关节炎患者中显著低于对照组。在转化生长因子-β1(+869T/C)方面，抗CCP抗体阳性患者CC基因型频率显著低于抗CCP抗体阴性患者。此外，IL-10(−592)CC和(−819)CC可能与生物学上的DMARD应答有关。我们的结果表明，细胞因子编码基因的多态性分析可能有助于日本类风湿关节炎患者的治疗选择。
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. 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. 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. Our results suggest that the analysis of polymorphisms in cytokine-encoding genes may be useful when selecting treatment for Japanese RA patients.