Lack of association of –863C/A (rs1800630) polymorphism of tumor necrosis factor-α gene with rheumatoid arthritis

Abstract

IntroductionMultifunctional 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.Material and methodsA 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 χ2/Fisher’s exact test using GraphPad prism 6 software.ResultsWe found that the TNF-α –863 C/A (rs1800630) variant was not differentially segregated between cases and controls in either genotype frequency, with χ2 of 2.771 and a p-value of 0.2502, or allele frequency, with χ2 of 2.741 and a p-value of 0.0978, with an odds ratio (95% CI) of 0.7490 (0.5317–1.055).ConclusionsThe 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.

Association of tumor necrosis factor-alpha promoter region gene polymorphism at positions -308G/A, -857C/T, and -863C/A with etanercept response in Iraqi rheumatoid arthritis patients

“…However, in two studies involving RA patients from northwest China's Han population 48 and Thai RA patients, 49 TNF-a -863C/A was strongly associated with RA susceptibility. Nevertheless, this association was not confirmed in another Pakistani study, 50 or the results showed a weak association in the North Indian population study. 51 The present study findings can be explained by the fact that carriers of the rare -863AA genotype had lower serum TNF-a levels and a significant change in DAS28 than carriers of the CC genotype.…”

Foot static disturbances and clinical features in overweight patients with rheumatoid arthritis

“…There are studies describing the application of plantography examinations in detection of foot disturbances in RA patients [17,20]. Researchers indicate that the results of plantography are precise and comparable [20][21][22][23].…”

Association of TNF-α-308G/A, -238G/A, -863C/A, -1031T/C, -857C/T polymorphisms with periodontitis susceptibility

“…TNF-863A allele lessened the NF-κB p50/p50 binding that directed the enhanced TNF production in human monocytes. [ 41 ] In 2003, Soga's study demonstrated that −863C/A A allele was a risk factor for CP. [ 32 ] These meaned -863C/A gene polymorphism may have impact on disease.…”