TNF-alpha gene polymorphisms can help to predict response to etanercept in psoriatic patients.
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.


OBJECTIVE
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.


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 (SNPs) 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.


CONCLUSIONS
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.
Department of Dermatology, Catholic University of the Sacred Heart, Rome, Italy.
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C
De Simone
Institute of General Pathology, Catholic University of the Sacred Heart, Rome, Italy.
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M
Farina
Department of Dermatology, Catholic University of the Sacred Heart, Rome, Italy.
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Maiorino
Institute of General Pathology, Catholic University of the Sacred Heart, Rome, Italy.
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C
Fanali
Department of Dermatology, Catholic University of the Sacred Heart, Rome, Italy.
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F
Perino
Institute of General Pathology, Catholic University of the Sacred Heart, Rome, Italy.
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A
Flamini
Department of Dermatology, Catholic University of the Sacred Heart, Rome, Italy.
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G
Caldarola
Institute of General Pathology, Catholic University of the Sacred Heart, Rome, Italy.
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A
Sgambato
D015535:Arthritis, Psoriatic / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D000068800:Etanercept / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D013053:Spectrophotometry; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D004247:DNA; D000068800:Etanercept