Das Somdatta, Baruah Chitralekha, Saikia Anjan Kumar, Tiwari Diptika, Bose Sujoy
Department of Bioengineering and Technology, Gauhati University, Guwahati 781 014, India.
J Genet. 2019 Mar;98.
Antitumour necrosis factor-alpha (TNF-α) therapy is used as a clinical intervention for rheumatoid arthritis (RA) but differences exist in response to the treatment which makes the candidature of the screening of TNF-α alteration(s) at genetic and expression levels an important agenda prior to treatment. This study aims to determine the associative role of TNF-α -308G/A polymorphism and differential expression of TNF-α in the pathogenesis of RA. A case-control study where a total of 126 RA patients were enrolled based on ACR-EULAR (2010) criteria, along with 160 community matched age and sex controls over a period of three years. The differential expression level of TNF-α mRNA and protein level was studied and TNF-α -308G/A polymorphism was screened by T-ARMS PCR assay. All statistical analysis was performed using SPSS software. mRNA expression level of TNF-α was upregulated in RA cases (avg. 15.85 ± 9.52 fold) compared to control. TNF-α protein level was found to be higher in RA cases (28.62±7.17 pg/mL) compared to control (23.14±6.91 pg/mL). TNF-α -308 variant GA genotype was higher in RA (46.03%) than in control (25%). The presence of TNF-α -308 variant A allele was associated with increased risk of RA susceptibility (odds ratio (OR) = 2.559 at 95% confidence interval (CI), 0.001) but not severity (OR = 1.617 at 95% CI, = 0.571). The presence of -308 variant genotype was associated with a higher TNF-α mRNA and protein expression. The presence of TNF-α -308A allele is associated with increased risk of RA susceptibility and differential TNF-α expression, and has prognostic significance. Association of higher TNF-α pro-inflammatory cytokine levels with northeast Indian patients makes them suitable subjects for anti-TNF-α therapy.
抗肿瘤坏死因子-α（TNF-α）疗法被用作类风湿性关节炎（RA）的临床干预手段，但对该治疗的反应存在差异，这使得在基因和表达水平上筛查TNF-α改变的候选情况成为治疗前的一项重要议程。本研究旨在确定TNF-α -308G/A多态性与TNF-α差异表达在RA发病机制中的关联作用。这是一项病例对照研究，在三年时间里，共纳入了126例根据美国风湿病学会-欧洲抗风湿病联盟（ACR-EULAR，2010年）标准确诊的RA患者，以及160名年龄和性别相匹配的社区对照者。研究了TNF-α mRNA和蛋白水平的差异表达，并通过T-ARMS PCR检测法筛查了TNF-α -308G/A多态性。所有统计分析均使用SPSS软件进行。与对照组相比，RA病例中TNF-α的mRNA表达水平上调（平均15.85±9.52倍）。发现RA病例中TNF-α蛋白水平（28.62±7.17 pg/mL）高于对照组（23.14±6.91 pg/mL）。RA中TNF-α -308变异体GA基因型（46.03%）高于对照组（25%）。TNF-α -308变异体A等位基因的存在与RA易感性风险增加相关（95%置信区间（CI）下的优势比（OR）=2.559，P = 0.001），但与疾病严重程度无关（95% CI下的OR = 1.617，P = 0.571）。-308变异基因型的存在与更高的TNF-α mRNA和蛋白表达相关。TNF-α -308A等位基因的存在与RA易感性风险增加及TNF-α差异表达相关，且具有预后意义。较高的TNF-α促炎细胞因子水平与印度东北部患者的相关性使他们成为抗TNF-α治疗的合适对象。
