Abstract
Aims: To investigate whether variants of MTHFR, TYMS and SLCO1B1 are associated with ALT elevation in rheumatoid arthritis patients starting methotrexate (MTX). Patients & methods: Clinical and laboratory data were collected from the start of MTX treatment. Genotyping of MTHFR, TYMS and SLCO1B1 was performed. Univariate and multiple logistic regression were used for statistical analysis. Results: 34 out of 369 patients experienced ALT >1.5 × ULN less than 6 months from start. MTHFR A1298C (rs1801131) was nominally associated with an ALT >1.5 × ULN within 6 months after the start of MTX (OR = 1.7 [95% CI: 1.04–2.9]; p = 0.03), but did not pass correction for multiple testing. A multiple model containing MTHFR 1298C and clinical factors predicted the outcome (C-statistic 0.735). TYMS and SLCO1B1 were not associated with the outcome. Conclusions: A model containing MTHFR 1298C and clinical factors might predict risk of early ALT elevation.
Financial & competing interests disclosure
This work was supported by the Agnes and Mac Rudberg Foundation; the Swedish Research Council (Medicine 521-2011-2440, 521-2014-3370 and 2018-03307); Swedish Heart and Lung Foundation (no. 20120557, 20140291 and 20170711); Selander’s Foundation; Thuréus’ Foundation; the Swedish Medical Products Agency; and the Clinical Research Support (Avtal om Läkarutbildning och Forskning, ALF) at Uppsala University. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.