Open AccessGenome-wide association study of liver enzyme elevation in rheumatoid arthritis patients starting methotrexate
Author(s) -
Johanna Karlsson Sundbaum,
Eva Baecklund,
Niclas Eriksson,
Hugo Kohnke,
Matilda Wallenberg,
Marco Cavalli,
Claes Wadelius,
Mia Wadelius,
Pär Hallberg
Publication year - 2021
Publication title -
pharmacogenomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.541
H-Index - 91
eISSN - 1744-8042
pISSN - 1462-2416
DOI - 10.2217/pgs-2021-0064
Subject(s) - rheumatoid arthritis , methotrexate , linkage disequilibrium , medicine , genome wide association study , pathogenesis , genetic association , janus kinase , allele , genetics , gene , biology , genotype , receptor , single nucleotide polymorphism , haplotype
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.