Genome-wide association study of liver enzyme elevation in rheumatoid arthritis patients starting methotrexate

Aim: To identify novel genetic variants predisposing to elevation of Alanine aminotransferase (ALT) in rheumatoid arthritis (RA) patients after initiation of methotrexate (MTX) treatment. Patients & methods: We performed genome-wide association studies in 198 RA patients starting MTX. Outcomes were maximum level of ALT and ALT >1.5-times the upper level of normal within the first 6 months of treatment. Results: RAVER2 (rs72675408) was significantly associated with maximum level of ALT (p = 4.36 x 10(-8)). This variant is in linkage disequilibrium with rs72675451, which is associated with differential expression of JAK1 and RAVER2. Conclusion: We found an association between ALT elevation and genetic variants that may regulate the expression of JAK1 and RAVER2. JAK1 encodes a janus kinase involved in the pathogenesis of RA.

Automated summary

The study identified novel genetic variants associated with elevation of Alanine aminotransferase (ALT) in rheumatoid arthritis (RA) patients after methotrexate (MTX) treatment, showing a potential link to the expression of JAK1 and RAVER2, genes involved in the pathogenesis of RA.