TNF‐alpha gene polymorphisms can help to predict response to etanercept in psoriatic patients. (26th February 2015)

• Record Type: Journal Article
• Authors: De Simone, C.; Farina, M.; Maiorino, A.; Fanali, C.; Perino, F.; Flamini, A.; Caldarola, G.; Sgambato, A.
• Is Part Of: Journal of the European Academy of Dermatology and Venereology. Volume 29:Number 9(2015:Sep.)
• Page Start: 1786
• Page End: 1790
• Publication Date: 2015-02-26
• Subjects: Dermatology -- Periodicals; Sexually transmitted diseases -- Periodicals; 616.5
• DOI: 10.1111/jdv.13024
• Languages: English
• ISSNs: 0926-9959

Abstract

<abstract abstract-type="main" id="jdv13024-abs-0001"> <title>Abstract</title> <sec id="jdv13024-sec-0001" sec-type="section"> <title>Background</title> <p>Genetic factors might have a role for lack of therapeutic response to anti‐TNF‐alpha agents, as previously suggested in patients with rheumatoid arthritis and inflammatory bowel disease.</p> </sec> <sec id="jdv13024-sec-0002" sec-type="section"> <title>Objectives</title> <p>We evaluated the role of the main TNF‐alpha polymorphisms (−238G>A, −308G>A, −857C>T) in predicting the response to etanercept, an anti‐TNF‐alpha fusion protein.</p> </sec> <sec id="jdv13024-sec-0003" sec-type="section"> <title>Material and Methods</title> <p>Genomic DNA was extracted from buccal epithelial cells in a series of 97 psoriatic patients who received etanercept for at least 3 months. Patients were classified as responders, if they achieved a PASI improvement ≥75% after 12 weeks of etanercept treatment, and non‐responders, if PASI improvement was <75%. Single‐nucleotide polymorphisms (SNPs) in TNF‐alpha gene (−238G>A, −308G>A, −857C>T) were genotyped by PCR restriction fragment length polymorphism (RFLP) assays.</p> </sec> <sec id="jdv13024-sec-0004" sec-type="section"> <title>Results</title> <p>We found that patients heterozygous (GA) for the −238G>A polymorphism were more likely not responsive to therapy compared to the GG genotype. In fact, the GA genotype was found in 5/59 (8·5%) responders and in 14/38 (36·8%) non‐responders (<italic>P</italic> = 0·001). A significant relationship with therapy was also observed for the –308G>A polymorphisms. In fact, the GG, GA and AA genotypes were detected in 48 (81·4%), 9 (15·3%) and 2 (3·4%) of the 59 responders and in 22 (57·9%), 11 (28·9%) and 5 (13·2%) of the 38 non‐responder patients (<italic>P</italic> = 0·03). No association with therapy was observed for the −857C>T polymorphisms.</p> </sec> <sec id="jdv13024-sec-0005" sec-type="section"> <title>Conclusion</title> <p>Our study supports the role of TNF‐alpha polymorphisms in predicting the response to anti‐TNF‐alpha agents. In particular, we found that the presence of −238G>A and −308G>A polymorphisms is associated with poor response to a 3‐month therapy with etanercept. However, our data have yet to be validated in larger cohorts.</p> </sec> </abstract>