Genome-wide association analysis of psoriasis patients treated with anti-TNF drugs

Abstract

While anti-TNF therapies are effective against psoriasis, 30%–50% of patients do not show an adequate response to these rugs. Different candidate-gene pharmacogenetics studies have identified single nucleotide polymorphisms that may predict anti-TNF drugs response in psoriasis. Nevertheless, only one paper has undertaken a pharmacogenomic approach failing to find significant biomarkers of biological drug response along the whole genome. Furthermore, most of the pharmacogenetic candidate biomarkers identified previously have not been confirmed in a different cohort of patients. The objective of this study was to find biomarkers that could predict anti-TNF drugs response along the whole genome and validate biomarkers identified previously. A genome-wide association study (GWAS) was performed using the Human Omni Express-8 v1.2 Beadchips in 243 psoriasis patients treated with anti-TNF drugs. This study was multicentric and did not interfere with clinical practice. Associations between single nucleotide polymorphisms (SNP) and PASI75 (a 75% reduction with respect to baseline PASI) at 3 months were evaluated. Imputation was performed using SNPs with R2 > 0.7. There were two SNPs located in NPFFR2 that were close to the significant threshold of 5 × 10−8. These data suggest that NPFFR2 might be associated with anti-TNF drug response. However, further studies involving a larger cohort of patients are needed in order to confirm these results.