Whole exome sequencing (WES) of methotrexate response/adverse event profile in rheumatoid arthritis patients

摘要

Aim of the workTo 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 methodsThe 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 identifiedResultsThe 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.ConclusionIn 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.