Sadaf Tayyaba, John Peter, Bhatti Attya, Malik Javaid M
Department of Health Care Biotechnology, Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Islamabad, Pakistan.
Arthritis Research Center, Rahmat Noor Clinic, Rawalpindi, Pakistan.
Arch Med Sci. 2019 Mar;15(2):531-536. doi: 10.5114/aoms.2018.76946. Epub 2018 Jul 5.
Multifunctional pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) has been implicated in a variety of inflammatory diseases including rheumatoid arthritis (RA). TNF-α polymorphisms are mostly located in its promoter region and play a significant role in disease susceptibility and severity. We therefore sought to investigate TNFA -863C/A (rs1800630) polymorphism association with RA activity in our Pakistani study group.
A total of 268 human subjects were enrolled. Among them, 134 were RA patients and 134 were controls. In this study the physical parameters of RA patients were collected, and the disease activity was measured by DAS28. The genotypes were determined following the allele-specific PCR along with the pre-requisite internal amplification controls. Subsequently, data were analyzed statistically for any significant association including χ/Fisher's exact test using GraphPad prism 6 software.
We found that the TNF-α -863 C/A (rs1800630) variant was not differentially segregated between cases and controls in either genotype frequency, with χ of 2.771 and a -value of 0.2502, or allele frequency, with χ of 2.741 and a -value of 0.0978, with an odds ratio (95% CI) of 0.7490 (0.5317-1.055).
The lack of positive association of TNF-α -863(rs1800630) polymorphism in our study group implies that TNF-α -863 polymorphism is not a susceptible marker to RA and cannot serve as a genetic factor for screening RA patients in Pakistan. There might be other factors that may influence disease susceptibility. However, further investigations on additional larger and multi-regional population samples are required to determine the consequences of genetic variations for disease prognosis.
多功能促炎细胞因子肿瘤坏死因子-α（TNF-α）与包括类风湿性关节炎（RA）在内的多种炎症性疾病有关。TNF-α多态性大多位于其启动子区域，在疾病易感性和严重程度中起重要作用。因此，我们试图在我们的巴基斯坦研究组中研究TNFA -863C/A（rs1800630）多态性与RA活动的关联。
共纳入268名人类受试者。其中，134名是RA患者，134名是对照。在本研究中，收集了RA患者的身体参数，并通过DAS28测量疾病活动度。基因型通过等位基因特异性PCR以及必要的内部扩增对照来确定。随后，使用GraphPad prism 6软件对数据进行统计学分析，以确定包括χ²/费舍尔精确检验在内的任何显著关联。
我们发现，TNF-α -863 C/A（rs1800630）变体在病例组和对照组之间的基因型频率（χ²为2.771，P值为0.2502）或等位基因频率（χ²为2.741，P值为0.0978）上没有差异分离，优势比（95%置信区间）为0.7490（0.5317 - 1.055）。
我们研究组中TNF-α -863（rs1800630）多态性缺乏正相关，这意味着TNF-α -863多态性不是RA的易感标志物，不能作为在巴基斯坦筛查RA患者的遗传因素。可能有其他因素影响疾病易感性。然而，需要对更多更大规模的多区域人群样本进行进一步研究，以确定基因变异对疾病预后的影响。
