期刊
PHARMACOGENOMICS
卷 23, 期 15, 页码 813-820出版社
FUTURE MEDICINE LTD
DOI: 10.2217/pgs-2022-0074
关键词
adverse reactions; drug-related side effects; genome-wide association study; hepatotoxicity; methotrexate; pharmacogenetics; rheumatoid arthritis
资金
- Agnes Foundation at Uppsala University
- Mac Rudberg's Foundation at Uppsala University
- Brunnberg's Foundation at Uppsala University
- Selander's Foundation at Uppsala University
- Thureu's Foundation at Uppsala University
- Swedish Rheumatism Association
- Swedish Research Council [521-2011-2440, 521-2014-3370, 2018-03307]
- Swedish Heart-Lung Foundation [20120557, 20140291, 20170711]
- Clinical Research Support (Avtal om Lakarutbildning och Forskning, ALF) at Uppsala University
- Swedish Research Council [2018-03307] Funding Source: Swedish Research Council
- Vinnova [2018-03307] Funding Source: Vinnova
This study identified associations between single-nucleotide polymorphisms (SNPs) in genes related to male fertility and inflammatory processes and elevated alanine aminotransferase (ALT) levels through a genome-wide association study (GWAS).
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 x 10(-8)) and PLCG2 (rs60427389) was tentatively associated with ALT >1.5 x ULN. Conclusion: Associations with SNPs in genes related to male fertility (SPATA9) and inflammatory processes (PLCG2) were identified.
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