Impact of TNF-α and TNFR1B genes polymorphisms on disease susceptibility and predict response to anti-TNF therapy in psoriatic patients

Abstract

Background: Polymorphisms of genes including tumor necrosis factor alpha (TNF-α) and Tumor necrosis factor receptor super family 1B (TNFRSF1B) may influence susceptibility to psoriasis as well as patients' biological responses. Aim of the study: To demonstrate the potential roles of TNF-α and TNFR1B, genes polymorphism {TNF-α -308 (G/A) and TNFR1B rs1061622 (T/C)} in susceptibility to psoriasis, elucidating their possible influence on patients' biological drug response and serum level. Subjects and methods: One hundred psoriatic patients and 100 apparently healthy individuals as a controls were included in this study. Restriction Fragment Length Polymorphism-Polymerase Chain Reaction (RFLP-PCR) was performed to evaluate different TNF-α and TNFR1B genes polymorphism. TNF-α and TNFR1B serum levels were assessed by enzyme linked immune sorbent assay. Results: Comparison between overall patients and controls revealed a higher serum level of TNF-α in patients than the controls with a highly significant difference (P<0.001). The risk of psoriasis was observed among people who had TNF-α-308 AA or GA genotypes, namely A allele-containing genotypes. Regarding the response to treatment it was revealed that the mutant homozygous genotype AA with higher frequency in non-responder (85.7%). The risk of non-response to biological drug was higher in people carrying AA genotype than in people carrying GG or GA genotypes. Concerning to serum level of tumor necrosis factor receptor super family member 1B (TNFRSF1B), Present study showed a highly significant difference between overall patients and controls. TNFSFR1B (rs1061622) SNP, CC and CT genotypes were dominant in controls and psoriatic patients, whereas the mutant TT genotype was dominant only in psoriatic patients. High risk of psoriasis in subjects had TT genotype than subjects carrying CC genotype. The response to treatment in the present study shows non-significant difference in the distribution of different genotypes of TNFSFR1B (rs1061622) polymorphism between responders and non-responders patients. Conclusion: These results may provide an additional evidence for association of TNF-α -308G/A and TNFRSF1B rs1061622, genes polymorphism to psoriasis susceptibility and disease severity and may serve as predictive and prognostic biomarkers.

The Impact of rs767455 and rs1061622 Polymorphisms on Treatment Outcomes in Iraqi Ankylosing Spondylitis Patients Taking Etanercept

“…The outcome seems to be in agreement with result of previous study done by Schiotis et al (25) and Xing-Rong et al (23) . However, the current findings disagree with Iraqi study done by Hadi et al (26) on psoriatic patients, which revealed heterozygote genotypes of TNFRSF1B SNP can predict a positive prognosis responsiveness to TNF-α inhibitors (26) . Considering investigating whether SNPs in the genes, which encodes TNFRSF1A/TNFRSF1B alter the severity of deleterious effects from ETN use, this study looked at the relationship between genotype and the occurrence of infection, injection site reaction, headache, and rash (adverse events associated with ETN use).…”

Genetic Influence on Treatment Response in Psoriasis: New Insights into Personalized Medicine

“…Conversely, Masouri et al found that the A-allele and not the C-allele in the TNFAIP3 rs610604 polymorphism was associated with a better response, which was only significant with Etanercept [ 90 ]. These findings are in line with those of an Iraqi study involving 100 patients with psoriasis [ 104 ]. Other authors have found no effect of TNFAIP3 SNPs in response to these drugs [ 83 , 99 ].…”

The Association between Genetics and Response to Treatment with Biologics in Patients with Psoriasis, Psoriatic Arthritis, Rheumatoid Arthritis, and Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis

“…In the meta-analysis, the minor allele of TNF-α-238 (rs361525) was found to be associated with poor response to etanercept (OR: 0.19 [95% CI: 0.08–0.47]) based on two studies (n = 151 patients [ 36 , 37 ]) but not when assessing all TNFi together. The minor alleles of TNF-α-308 (rs1800629) (four studies, n = 548 patients [ 24 , 36 , 37 , 38 ]) and TNF-α-857 (rs1799724) (four studies (n = 328 patients [ 36 , 37 , 39 , 40 ]) were associated with poor response to treatment with TNFi (OR: 0.41 [95% CI: 0.19–0.88], and OR: 0.53 [95% CI: 0.29–0.97], respectively). The association between SNPs in TNF receptors and response to TNFi was assessed in multiple studies.…”

“…The association between SNPs in TNF receptors and response to TNFi was assessed in multiple studies. Of these, the minor allele of TNFRSF1A (rs191190) was associated with good response to TNFi (OR: 2.86 [95% CI: 1.25–6.52]) based on two studies and 239 patients [ 32 , 41 ], while the minor alleles of TNFRSF1B (rs1061622) (six studies, n = 55,832, [ 38 , 39 , 40 , 41 , 42 ]) and TNFRSF1A (rs4149570) two studies, n = 23,932, [ 41 ]) were associated with poor response to treatment with TNFi (OR: 0.49 [95% CI: 0.30–0.79] and OR: 0.51 [95% 0.29–0.89], respectively).…”