Department of Rheumatology, National University of Medical Sciences, Rawalpindi, Pakistan.
Cancer Genetics and Epigenetics Lab, Department of Biosciences, COMSATS University, Islamabad, Pakistan.
Mol Biol Rep. 2021 Jun;48(6):5171-5180. doi: 10.1007/s11033-021-06518-3. Epub 2021 Jul 1.
Rheumatoid arthritis (RA) is one of the most common autoimmune diseases globally, and is an important public health concern, associating with early death and systemic complications. Although key development in RA treatment has already been made still RA affected individuals face comorbidity and disability. Therefore, there is a need to discover new risk factors in helping early diagnosis and treatment of RA. The present study is designed to assess the variations of Vitamin D receptor (VDR) and interleukin -6 (IL-6) in RA patients. Polymorphisms of said genes were calculated in 300 RA patients and 300 controls, using Tetra-ARMS polymerase chain reaction. Secondly, expression levels of selected genes were checked using the quantitative PCR (qPCR) and obtained results were evaluated using a different statistical test. Logistic regression analysis showed that frequency of mutant allele of VDR gene polymorphisms (rs11168268, OR = 4.84; 95% CI = 2.94-7.97; p = 0.0001; rs2248098, OR = 1.65; 95% CI = 1.07-2.54; p = 0.02) and IL-6 gene polymorphisms (rs184229712, OR = 2.47; 95% CI = 1.56-3.92, p = 0.0001; rs36215814, OR = 2.14; 95% CI = 1.30-3.53; p = 0.002) was observed significantly higher in RA patients vs controls. Expression analysis showed the significant upregulation of IL-6 (p < 0.0001) and downregulation of VDR gene (p < 0.0001) in RA cases vs controls. ROC curve analysis showed that downregulation of IL-6 (AUC = 0.86, p < 0.001) and upregulation of VDR (AUC = 0.77, p < 0.001) was act as the good diagnostic marker for detection/diagnosis of arthritis. In conclusions, data from the present study showed the significant involvement of VDR and IL-6 gene variations in RA pathogenesis.
类风湿关节炎（RA）是全球最常见的自身免疫性疾病之一，也是一个重要的公共卫生关注点，与早期死亡和全身并发症相关。尽管 RA 治疗已经取得了重大进展，但 RA 患者仍然面临合并症和残疾的问题。因此，需要发现新的风险因素，以帮助早期诊断和治疗 RA。本研究旨在评估维生素 D 受体（VDR）和白细胞介素-6（IL-6）在 RA 患者中的变化。使用 Tetra-ARMS 聚合酶链反应计算了 300 名 RA 患者和 300 名对照者的上述基因多态性。其次，使用定量 PCR（qPCR）检查选定基因的表达水平，并使用不同的统计检验评估获得的结果。逻辑回归分析显示，VDR 基因多态性（rs11168268，OR=4.84；95%CI=2.94-7.97；p=0.0001；rs2248098，OR=1.65；95%CI=1.07-2.54；p=0.02）和 IL-6 基因多态性（rs184229712，OR=2.47；95%CI=1.56-3.92，p=0.0001；rs36215814，OR=2.14；95%CI=1.30-3.53；p=0.002）的突变等位基因频率在 RA 患者中明显高于对照组。表达分析显示，与对照组相比，RA 病例中 IL-6（p<0.0001）显著上调，而 VDR 基因表达下调（p<0.0001）。ROC 曲线分析显示，IL-6 下调（AUC=0.86，p<0.001）和 VDR 上调（AUC=0.77，p<0.001）可作为关节炎检测/诊断的良好诊断标志物。总之，本研究数据表明，VDR 和 IL-6 基因变异在 RA 发病机制中具有重要作用。
