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

Abstract

Objectives: This study aims to evaluate the association between polymorphisms in the promoter region of the tumor necrosis factor-alpha (TNF-α) gene at locations -308G/A, -857C/T, and -863C/A with the tendency of being non-responder to etanercept. Patients and methods: Between October 2020 and August 2021, a total of 80 patients (10 males, 70 females; mean age: 50 years; range, 30 to 72 years) with rheumatoid arthritis (RA) receiving etanercept for at least six months were included. The patients were divided into two groups responders and non-responders, based on their response after six months of continuous treatment. Following polymerase chain reaction amplification of the extracted deoxyribonucleic acid, sequencing by Sanger method was performed to identify the polymorphism at the TNF-α promoter region. Results: In the responder group, the GG genotype of (-308G/A) and the AA genotype of (-863C/A) were both significantly present. The CC genotype of (-863C/A) was significantly present in the non-responders group. The CC of (-863C/A) SNP was the only genotype that appeared to increase the likelihood of being resistant to etanercept. The GG genotype of (-308G/A) was negatively correlated with the likelihood of being a non-responder. The (-857CC) and (-863CC) genotypes were significantly more prevalent in the non-responders group. Conclusion: The presence of the (-863CC) genotype, alone or in combination with (-857CC), is linked to an increased likelihood of becoming a nonresponder to etanercept. The GG genotype of -308G/A and the AA genotype of -863C/A significantly increase the likelihood of becoming responder to etanercept.

Biogenetic Markers for Predicting Response to Immunotherapy in Rheumatoid Arthritis

“…Our findings are consistent with the findings of [9] metaanalyses, which found no significant difference in the percentage of A allele carriers between groups that responded to treatment and those that did not. In a crosssectional investigation of 80 Iraqi RA patients treated with ETN, [33] discovered no significant difference in the availability of GA and AA genotypes of the -308G/A polymorphism between responsive and non-responsive groups. Our findings, on the other hand, contradict three prior studies that found a link between TNF-308 GG genotype and improved response to IFX, ETN, and ADA in RA patients [34]- [36].…”

The Association of Genetic Polymorphisms in Tumor Necrosis Factor-Alpha and Interleukins with Disease Severity or Response to Biological Therapy in Iraqi Rheumatoid Arthritis Patients: A Narrative Review

“…The impact of the -308G/A polymorphism on TNFα blocker responsiveness as well as the impact of these polymorphisms on heightened susceptibility to and severity of RA were examined in several studies [65][66][67]. Results showed no significant difference in the availability of GA and AA genotypes of the -308G/A polymorphism between responsive and non-responsive groups, in contrast to the study by Mohammed et al [9]. The responsive group, however, had a considerably higher presence of the GG genotype.…”

“…According to a meta-analysis of earlier research, patients homozygous for the G allele respond better to anti-TNF-α therapy than those who carry the A allele at TNF-α-308 [54]. Numerous studies conducted in Iraq [9,11,14,16,18,19] on the genotype distribution for -308 G/A found that the GG genotype predominated in nearly three-quarters of the population, followed by heterozygote GA and homozygote AA. Additionally, whereas the A allele was present in a minor proportion of individuals, the G allele was detected in the majority of RA patients.…”

“…Using epigenetic research, high-resolution mapping of open chromatin, chromosomal conformation technologies, and other techniques, many of the gaps between genetic risk variations and causal genetic components can now be filled in, furthering our understanding of RA genetics [7]. The association between various genotypes of many variations and the propensity to be non-responsive to biological therapy or the severity of RA disease has been the subject of numerous research [8][9][10]. However, the majority of these studies' conclusions were contradictory [8][9][10], and the only striking and statistically supported finding regarding the reasons for the inadequate response to TNF-α blockers is the current smoking status of RA patients [11][12][13].…”

“…The association between various genotypes of many variations and the propensity to be non-responsive to biological therapy or the severity of RA disease has been the subject of numerous research [8][9][10]. However, the majority of these studies' conclusions were contradictory [8][9][10], and the only striking and statistically supported finding regarding the reasons for the inadequate response to TNF-α blockers is the current smoking status of RA patients [11][12][13]. In this review, we will look at the distribution of genetic variants in tumor necrosis factor-alpha and interleukins in Iraqi rheumatoid arthritis patients and how these polymorphisms relate to the severity of the disease or the effectiveness of biological therapy.…”