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Future Medicine, Pharmacogenomics, 15(23), p. 813-820, 2022

DOI: 10.2217/pgs-2022-0074

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Genome-wide association study of liver enzyme elevation in an extended cohort of rheumatoid arthritis patients starting low-dose methotrexate

Journal article published in 2022 by Marco Cavalli ORCID, Niclas Eriksson ORCID, Johanna Karlsson Sundbaum ORCID, Matilda Wallenberg, Hugo Kohnke, Eva Baecklund, Pär Hallberg ORCID, Mia Wadelius ORCID
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Aim: A follow-up genome-wide association study (GWAS) in an extended cohort of rheumatoid arthritis (RA) patients starting low-dose methotrexate (MTX) treatment was performed to identify further genetic variants associated with alanine aminotransferase (ALT) elevation. Patients & methods: A GWAS was performed on 346 RA patients. Two outcomes within the first 6 months of MTX treatment were assessed: ALT >1.5-times the upper level of normal (ULN) and maximum level of ALT. Results: SPATA9 (rs72783407) was significantly associated with maximum level of ALT (p = 2.58 × 10-8) and PLCG2 (rs60427389) was tentatively associated with ALT >1.5 × ULN. Conclusion: Associations with SNPs in genes related to male fertility ( SPATA9) and inflammatory processes ( PLCG2) were identified.