The TNFRSF1B rs1061622 polymorphism (p.M196R) is associated with biological drug outcome in Psoriasis patients

Abstract

Genetic factors are involved not only in the overall risk of suffering psoriasis, but also in their clinical characteristics and eventually in drug outcome. Biological therapies have dramatically improved the prognosis of Psoriasis. However, these treatments are very expensive and patients often exhibit a heterogeneous response that could be partially attributed to their genetic background. Thus, the research for genetic markers in psoriatic patients that could predict a poor response to biological therapies is an important issue. Our aim was to evaluate the effect of DNA variants at the "TNFα pathway" that could affect the risk of developing Psoriasis or the response to biological therapies among these patients. The genetic association study included a total of 518 Psoriatic patients and 480 healthy controls. Ninety of these patients received biological treatment and based on the change in the PASI score after 24 weeks were classified as good (PASI score ≥75%), intermediate (PASI 50-75), and non-responders (PASI <50). Next generation sequencing (NGS) with semiconductor-array technology was used to identify the nucleotide variants in the TNF α, TNFRSF1A and TNFRSF1B, and we only found three missense amino acid changes, all in TNFRSF1B. Interestingly, we found a significantly higher frequency of rs1061622 G carriers among CW6-positive patients (p = 0.004; OR = 1.69, 95% CI = 1.18-2.41). Allele G (p.196R) carriers were significantly more frequent in the non-responder group (56%) (p = 0.05). In conclusion, we report a significant association between the TNFRSF1B p.M196R variant and the risk for psoriasis and the response to treatment with anti-TNF or anti-Il-12/Il-23. The genotyping of this polymorphism could help to optimize the treatment by identifying patients with a likely poor response to biological drugs.

Associations between functional polymorphisms and response to biological treatment in Danish patients with psoriasis

“…[33][34][35][36][37][38][39][40][41][42][43] For all significant associations, except TLR9 (rs352139) and LY96 (rs11465996), similar tendencies were observed for ORs for each of the anti-TNF agents (data available on request). To our knowledge, this is one of the largest cohorts for evaluation of response in patients treated with ustekinumab 44,45 and the second largest for evaluation of anti-TNF; only a Canadian study (also involving treatment primarily for psoriatic arthritis) had more patients.…”

Genetic Influences on Pharmacological Interventions in Psoriasis

“…The TNFRSF1B rs1061622 G allele was increased in frequency among HLA-Cw6 positive psoriasis patients [33]. There was also an increased risk for negative response to biological therapy in individuals with this allele [33]. This finding seems to conflict the results in another study, which stated that the TNFRSF1B SNP rs1061622 can predict good response to etanercept, but not to infliximab or adalimumab [34].…”

“…The polymorphism 676 T>G is associated with higher whole blood TNF-alpha production and was associated with positive response to etanercept (P=0.001) [31]. The TNFRSF1B rs1061622 G allele was increased in frequency among HLA-Cw6 positive psoriasis patients [33]. There was also an increased risk for negative response to biological therapy in individuals with this allele [33].…”

“…There was a noteworthy association of the TNFRSF1B SNP rs1061622 G allele and HLA-Cw6. Psoriasis patients with both HLA-Cw6 and rs1061622 G allele were at an increased risk for negative response to biologics, including ustekinumab [33]. Lastly, a study looked at SNPS in IL-17A and IL17F in regards to response to ustekinumab [43].…”

“…[33] TNFRSF1B rs1061622 This polymorphism in tumor necrosis factor receptor II is associated with higher whole blood TNF-α production.…”