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

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posted on 2022-09-07, 17:25 authored by Marco Cavalli, Niclas Eriksson, Johanna Karlsson Sundbaum, Matilda Wallenberg, Hugo Kohnke, Eva Baecklund, Pär Hallberg, Mia Wadelius

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.

Funding

This work was supported by the Agnes and Mac Rudberg’s, Brunnberg’s, Selander’s and Thure´us’ Foundations at Uppsala University; Swedish Rheumatism Association; Swedish Research Council (Medicine 521-2011-2440, 521-2014-3370 and 2018-03307); Swedish Heart-Lung Foundation (20120557, 20140291 and 20170711); and Clinical Research Support (Avtal om La¨ karutbildning och Forskning, ALF) at Uppsala University.

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