Medical Genetics Laboratory, Department of Neuroscience and Rehabilitation, University of Ferrara, 44121 Ferrara, Italy.
Laboratory of Immunorheumatology and Tissue Regeneration, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy.
Int J Mol Sci. 2023 Feb 18;24(4):4110. doi: 10.3390/ijms24044110.
Rheumatoid arthritis (RA) is an inflammatory autoimmune disease with a prevalence of 1%. Currently, RA treatment aims to achieve low disease activity or remission. Failure to achieve this goal causes disease progression with a poor prognosis. When treatment with first-line drugs fails, treatment with tumor necrosis factor-α (TNF-α) inhibitors may be prescribed to which many patients do not respond adequately, making the identification of response markers urgent. This study investigated the association of two RA-related genetic polymorphisms, c.665C>T (historically referred to as C677T) and c.1298A>C, in the gene as response markers to an anti-TNF-α therapy. A total of 81 patients were enrolled, 60% of whom responded to the therapy. Analyses showed that both polymorphisms were associated with a response to therapy in an allele dose-dependent manner. The association for c.665C>T was significant for a rare genotype ( = 0.01). However, the observed opposite trend of association for c.1298A>C was not significant. An analysis revealed that c.1298A>C, unlike c.665C>T, was also significantly associated with the drug type ( = 0.032). Our preliminary results showed that the genetic polymorphisms in the gene were associated with a response to anti-TNF-α therapy, with a potential significance for the anti-TNF-α drug type. This evidence suggests a role for one-carbon metabolism in anti-TNF-α drug efficacy and contributes to further personalized RA interventions.
类风湿关节炎（RA）是一种炎症性自身免疫性疾病，患病率为 1%。目前，RA 的治疗目标是实现低疾病活动度或缓解。如果未能达到这一目标，疾病会进展，预后较差。当一线药物治疗失败时，可能会开肿瘤坏死因子-α（TNF-α）抑制剂进行治疗，但许多患者对此治疗反应不足，因此迫切需要确定反应标志物。本研究探讨了 RA 相关的两个基因遗传多态性 c.665C>T（历史上称为 C677T）和 c.1298A>C 与抗 TNF-α治疗反应的关系。共纳入 81 例患者，其中 60%对治疗有反应。分析表明，两种多态性均以等位基因剂量依赖性方式与治疗反应相关。c.665C>T 的罕见基因型与治疗反应显著相关（ = 0.01）。然而，c.1298A>C 的关联趋势则相反，且无统计学意义。分析显示，c.1298A>C 与 c.665C>T 不同，与药物类型也显著相关（ = 0.032）。我们的初步结果表明，基因中的遗传多态性与抗 TNF-α治疗反应相关，对 TNF-α 类药物具有潜在意义。这一证据表明，一碳代谢在抗 TNF-α药物疗效中起作用，并有助于进一步实现 RA 的个体化干预。
