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

Sundbaum JK, Baecklund E, Eriksson N, Kohnke H, Wallenberg M, Cavalli M, Wadelius C, Wadelius M, Hallberg P

Pharmacogenomics 22 (15) 973-982 [2021-10-00; online 2021-09-15]

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 × 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.

Bioinformatics Support for Computational Resources [Service]

NGI Uppsala (SNP&SEQ Technology Platform) [Service]

National Genomics Infrastructure [Service]

PubMed 34521259

DOI 10.2217/pgs-2021-0064

Crossref 10.2217/pgs-2021-0064