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Genetic prediction of the effectiveness of biologics for psoriasis treatment
Author(s) -
Nishikawa Rika,
Nagai Hiroshi,
Bito Toshinori,
Ikeda Tetsuya,
Horikawa Tatsuya,
Adachi Atsuko,
Matsubara Tsukasa,
Nishigori Chikako
Publication year - 2016
Publication title -
the journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.9
H-Index - 65
eISSN - 1346-8138
pISSN - 0385-2407
DOI - 10.1111/1346-8138.13412
Subject(s) - psoriasis , medicine , infliximab , genome wide association study , adalimumab , single nucleotide polymorphism , snp , psoriasis area and severity index , tumor necrosis factor alpha , tumor necrosis factor α , dermatology life quality index , oncology , dermatology , genotype , genetics , biology , gene
Anti‐tumor necrosis factor ( TNF )‐α therapy is used for the treatment of psoriasis, with varying outcomes. However, the specific cause of inadequate response or treatment failure remains unknown. The aim of the present study was to identify useful clinical biomarkers for predicting therapeutic responses or to serve as new drug targets for refractory psoriasis cases. We performed a genome‐wide association study ( GWAS ) of 65 psoriasis patients who were prospectively followed after beginning anti‐ TNF ‐α therapy using Human Omni Express‐8 v1.2 Beadchips. Patients were enrolled at the dermatology departments of Kobe University Hospital and six collaborative hospitals. Associations between single nucleotide polymorphisms ( SNP ) and changes in the Psoriasis Area and Severity Index ( PASI ) after 12 weeks of treatment were evaluated. After genome data collection and quality control, a total of 731 442 SNP s were identified in 65 Asian psoriasis patients who were treated with adalimumab or infliximab. Here, we present 10 SNP s, such as those in JAG 2 and ADRA 2A , that were associated with treatment responses to anti‐ TNF ‐α agents (strongest effect, P < 7.11E‐06). This is the first GWAS to examine SNP associated with treatment responses in psoriasis patients. In addition, we identified other SNP that exhibited potential associations with anti‐ TNF ‐α treatment response, which merit further study. Of these, rs11096957 on TLR 10 , which is associated with increased TNF ‐α production, was previously reported to be associated with treatment responses to TNF ‐α inhibitors.