Genome-wide Association Study of Methotrexate-Induced Liver Injury in Rheumatoid Arthritis Patients.

Hepatotoxicity is a serious adverse drug reaction related to methotrexate (MTX). However, the cause of drug-induced liver injury (DILI) is still unclear and unpredictable. Genetic risk factors may predispose for MTX-DILI.

Predictive genetic biomarkers for the efficacy of methotrexate in rheumatoid arthritis: a systematic review.

Multiple pharmacogenetic studies investigated the effectiveness of methotrexate. However, due to the use of nonvalidated outcomes, lack of validation or conflicting results it remains unclear if genetic markers can help to predict response to MTX treatment. Therefore, a systematic review was performed.

Validation of a clinical pharmacogenetic model to predict methotrexate nonresponse in rheumatoid arthritis patients.

Aim: To study the performance of a clinical pharmacogenetic model for the prediction of nonresponse in rheumatoid arthritis (RA) patients treated with methotrexate (MTX) in combination with other synthetic or biologic disease-modifying anti-rheumatic drugs . This prediction model includes gender, smoking status, rheumatoid factor positivity and four genetic variants in AMPD1 (rs17602729), ATIC (rs2372536), ITPA (rs1127354) and MTHFD1 (rs17850560).

Methods: A total of 314 RA patients from three Dutch studies were retrospectively included.

SLC04A1, SLC22A2 and SLC28A2 variants not related to methotrexate efficacy or toxicity in rheumatoid arthritis patients.

Aim: A third of rheumatoid arthritis patients discontinue methotrexate treatment due to inefficacy or toxic side effects. Recently, an association between SLC04A1 rs2236553, SLC22A2 rs624249 and rs316019, and SLC28A2 rs10519020 and rs1060896 with the efficacy and toxicity of methotrexate was reported. This study aims to replicate these findings in an independent cohort (n = 324).

Pathway analysis to identify genetic variants associated with efficacy of adalimumab in rheumatoid arthritis.

Aim: About 30% of rheumatoid arthritis patients have no clinical benefit from TNF inhibitors. Genome-wide association (GWA) and candidate gene studies tested several putative genetic variants for TNF inhibitor efficacy with inconclusive results. Therefore, this study applied a systematic pathway analysis.