Pharmacogenetic markers to predict the clinical response to methotrexate in south Indian Tamil patients with psoriasis

• Published in: European journal of clinical pharmacology 2017-08, Vol.73 (8), p.965-971
• Main Authors: Indhumathi, S., Rajappa, Medha, Chandrashekar, Laxmisha, Ananthanarayanan, P. H., Thappa, D. M., Negi, V. S.
• Format: Article
• Language: English
• Subjects: Adult; Biomarkers - analysis; Biomarkers - blood; Biomedical and Life Sciences; Biomedicine; Cornified Envelope Proline-Rich Proteins - genetics; Cytokines - blood; Cytokines - genetics; Drug therapy; European Continental Ancestry Group - genetics; Female; Forkhead Transcription Factors - genetics; Foxp3 protein; Genetic markers; Genotype; Genotype & phenotype; Heterogeneity; Histocompatibility antigen HLA; HLA-A2 Antigen - genetics; HLA-B Antigens - genetics; HLA-C Antigens - genetics; Humans; Immunosuppressive Agents - therapeutic use; India; Inflammation; Interferon; Interleukin 10; Interleukin 12; Interleukin 2; Interleukin 23; Interleukin 4; Male; Methotrexate; Methotrexate - therapeutic use; Middle Aged; Pharmacogenetics; Pharmacology/Toxicology; Population genetics; Psoriasis; Psoriasis - blood; Psoriasis - drug therapy; Psoriasis - genetics; Treatment Outcome
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/s00228-017-2255-x

Introduction Despite the advent of several new systemic therapies, methotrexate remains the gold standard for the treatment of moderate to severe psoriasis. However, there exists a significant heterogeneity in individual response to methotrexate. There are no consistently reliable markers to predict methotrexate treatment response till date. Objectives We aimed to demonstrate the association of certain genetic variants in the HLA (HLA-A2, HLA-B17, and HLA-Cw6) and the non-HLA genes including T-helper (Th)-1, Th-2, Th-17 cytokine genes (IFN-γ, IL-2, IL-4, IL-10, IL-12B, and IL-23R), and T-regulatory gene (FOXP3) with the methotrexate treatment response in South Indian Tamil patients with psoriasis. Methods Of the 360 patients recruited, 189 patients with moderate to severe psoriasis were treated with methotrexate. Of the 189 patients, 132 patients responded to methotrexate and the remaining 57 patients were non-responders. We analyzed the association of aforesaid polymorphisms with the methotrexate treatment outcome using binary logistic regression. Results We observed that there were significant differences between genotype frequencies of HLA-Cw6 and FOXP3 (rs3761548) among the responders compared to non-responders, with conservative estimation. We observed that pro-inflammatory cytokines such as IFN-γ, IL-2, IL-12, and IL-23 were markedly reduced with the use of methotrexate, in comparison to the baseline levels, while the plasma IL-4 levels were increased posttreatment. Conclusion Our results serve as preliminary evidence for the clinical use of genetic markers as predictors of response to methotrexate in psoriasis. This might aid in the future in the development of a point-of-care testing (POCT) gene chip, to predict optimal treatment response in patients with psoriasis, based on their individual genotypic profile.