Whole Exome Sequencing (WES) of Methotrexate Response/adverse Event Profile in Rheumatoid Arthritis Patients

Aim of the work: To preliminary study polymorphisms in a set of genes of relevance to methotrexate (MTX) response based on the Drug Bank database in Egyptian rheumatoid arthritis (RA) patients. Patients and methods: The study included 10 consecutive adult female RA patients categorized according their response and adverse events (AEs) to MTX; patients with good response, ACR50 after 4 weeks was considered. Variant Call Format files were annotated and filtered via Drug Bank (11/9/2017) database in MTX. Accordingly, the following set of genes most related for RA MTX response were considered: SLC16A1, SLC7A11, SLC22A7, TBXAS1, PTK2B, ABCC2, ABCC4, SNORD13G, SLCO3A1, ABCC1, SLC46A1, SARM1, ABCB1, SLC19A, ATIC and SLCO1C1. Human genome DNA was assessed using Ion Ampliseq Exome Panel. Single-nucleotide variants (SNVs) and short insertions/deletions were identified Results: The mean age of the patients was 39 +/- 12.5 years and disease duration 9.8 +/- 7.4 years. AEs were present in 4 (2 poor and 2 good responders). 6 patients showed a good response with no AEs. Of the 16 studied genes, 19 variants were revealed. 18 SNVs and one deletion were detected. The C allele of ABCB1 was dominant in 7 out of 8 good responders' (87.5%). The G of ATIC was present in 20% with AEs and poor response. The T and G of SLCO1C1 were in 60% of good responders . Conclusion: In Egyptian RA patients, there is evidence of a possible influence of a set of gene variants on the disease pathogenesis while others were related to MTX AEs and response. (C) 2021 Egyptian Society of Rheumatic Diseases. Publishing services provided by Elsevier B.V.