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TNF ‐alpha gene polymorphisms can help to predict response to etanercept in psoriatic patients
Author(s) -
De Simone C.,
Farina M.,
Maiorino A.,
Fanali C.,
Perino F.,
Flamini A.,
Caldarola G.,
Sgambato A.
Publication year - 2015
Publication title -
journal of the european academy of dermatology and venereology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.655
H-Index - 107
eISSN - 1468-3083
pISSN - 0926-9959
DOI - 10.1111/jdv.13024
Subject(s) - etanercept , medicine , psoriatic arthritis , genotype , rheumatoid arthritis , single nucleotide polymorphism , gastroenterology , tumor necrosis factor alpha , methotrexate , snp , immunology , gene , genetics , biology
Background 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. Objectives 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. Material and Methods 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 ( SNP s) in TNF ‐alpha gene (−238G>A, −308G>A, −857C>T) were genotyped by PCR restriction fragment length polymorphism ( RFLP ) assays. Results 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 ( P = 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 ( P = 0·03). No association with therapy was observed for the −857C>T polymorphisms. Conclusion 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.