College of Pharmacy, Chungbuk National University, Yeonje-ri, Osong-eup, Heungdeok-gu, Cheongju-si.
College of Pharmacy, Ajou University, Worldcup-ro, Yeongtong-gu, Suwon.
Pharmacogenet Genomics. 2022 Jan 1;32(1):10-15. doi: 10.1097/FPC.0000000000000446.
Nuclear factor of activated T cells C2 (NFATC2) is known as a member of the transcription family and enhances tumor necrosis factor-alpha (TNF-α) synthesis in human T cells at the gene transcription level. Although NFATC2 has a potential role in rheumatoid arthritis (RA) progression and treatment, no study has investigated the association between NFATC2 gene polymorphisms and response status in RA patients receiving TNF-α inhibitors. This study aimed to examine the effects of polymorphisms in NFATC2, a TNF-α transcription factor, on response to TNF-α inhibitors.
This prospective observational study was performed in two centers. Seven single nucleotide polymorphisms (SNPs) were investigated. Good responders were defined as patients with disease activity score (DAS)28 ≤3.2 after 6 months of treatment. Logistic regression analyses were used to investigate the association between genetic polymorphisms and response to the treatment. To test the model's goodness of fit, a Hosmer-Lemeshow test was performed.
This study included 98 patients, among whom 46 showed favorable responses to the treatment. Patients with hypertension revealed an approximately three-fold lower response to TNF-α inhibitors compared to those without hypertension (23.5 vs. 76.5%; P = 0.049). After adjusting for covariates, C allele carriers of NFATC2 rs3787186 exhibited approximately three-fold lower rates of treatment response compared to those with TT genotype (P = 0.037). The Hosmer-Lemeshow test showed that the fitness of the multivariable analysis model was satisfactory (χ2 = 9.745; 8 degrees of freedom; P = 0.283).
This study suggested an association between the C allele of rs3787186 and treatment response in RA patients receiving TNF-α inhibitors.
核因子活化 T 细胞 C2（NFATC2）是转录因子家族的成员之一，可在基因转录水平上增强人 T 细胞中肿瘤坏死因子-α（TNF-α）的合成。尽管 NFATC2 在类风湿关节炎（RA）的进展和治疗中具有潜在作用，但尚无研究探讨 NFATC2 基因多态性与接受 TNF-α 抑制剂治疗的 RA 患者的反应状态之间的关系。本研究旨在研究 TNF-α 转录因子 NFATC2 基因多态性对 TNF-α 抑制剂反应的影响。
本前瞻性观察性研究在两个中心进行。研究了 7 个单核苷酸多态性（SNP）。治疗 6 个月后疾病活动评分（DAS）28≤3.2 的患者被定义为良好应答者。采用 logistic 回归分析探讨遗传多态性与治疗反应之间的关系。为了检验模型的拟合优度，进行了 Hosmer-Lemeshow 检验。
本研究共纳入 98 例患者，其中 46 例对治疗有良好反应。与无高血压的患者相比，患有高血压的患者对 TNF-α 抑制剂的反应率约低 3 倍（23.5%比 76.5%；P=0.049）。在校正协变量后，NFATC2 rs3787186 的 C 等位基因携带者的治疗反应率约为 TT 基因型的 3 倍（P=0.037）。Hosmer-Lemeshow 检验显示多变量分析模型的拟合优度令人满意（χ2=9.745；8 个自由度；P=0.283）。
本研究提示 RA 患者接受 TNF-α 抑制剂治疗时，rs3787186 的 C 等位基因与治疗反应之间存在关联。
