Genome-wide association study of liver enzyme elevation in rheumatoid arthritis patients starting methotrexate-Reference-Cited by-同舟云学术

Genome-wide association study of liver enzyme elevation in rheumatoid arthritis patients starting methotrexate

Published:2021-10 Issue:15 Volume:22 Page:973-982
ISSN:1462-2416
Container-title:Pharmacogenomics
language:en
Short-container-title:Pharmacogenomics

Author:

Sundbaum Johanna Karlsson¹²^ORCID,Baecklund Eva¹,Eriksson Niclas³⁴^ORCID,Kohnke Hugo⁴,Wallenberg Matilda⁴⁵,Cavalli Marco⁶^ORCID,Wadelius Claes⁶^ORCID,Wadelius Mia⁴^ORCID,Hallberg Pär⁴^ORCID

Affiliation:

1. Department of Medical Sciences, Rheumatology, Uppsala University, SE-751 85, Uppsala, Sweden

2. Department of Health Sciences, Luleå University of Technology, SE-971 87, Luleå, Sweden

3. Uppsala Clinical Research center, SE-751 85, Uppsala, Sweden

4. Department of Medical Sciences, Clinical Pharmacogenomics & Science for Life Laboratory, Uppsala University, SE-751 85, Uppsala, Sweden

5. Svensk Dos AB, Box 2, SE-751 03, Uppsala, Sweden

6. Department of Immunology, Genetics & Pathology, & Science for Life Laboratory, Uppsala University, SE-751 22, Uppsala, Sweden

Abstract

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.

Funder

Reumatikerförbundet

Hjärt-Lungfonden

Diabetesförbundet

Avtal om Läkarutbildning och Forskning, Uppsala Universitet

Vetenskapsrådet

Agnes and Mac Rudberg's, Brunnberg's, Selander's and Thuréus' Foundations at Uppsala University

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

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