MTHFR, TYMS and SLCO1B1 polymorphisms and adverse liver effects of methotrexate in rheumatoid arthritis

• Aims: To investigate whether variants of MTHFR, TYMS and SLCO1B1 are associated with alanine aminotransferase (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 >1.5xULN less than 6 months from start. MTHFR A1298C (rs1801131) was nominally associated with an ALT > 1.5 xULN 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)

Nyckelord

liver toxicity

methotrexate

MTHFR

rheumatoid arthritis

transaminases

TYMS and SLCO1B1

Medical Science

Medicinsk vetenskap

Publikations- och innehållstyp

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