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Membrane‐Spanning Protein Genetic Polymorphisms Related to Methotrexate Therapeutic Outcomes in a Chinese Rheumatoid Arthritis Population
Author(s) -
Lv Shuang,
Fan Huizhen,
Yang Hui,
Huang Jing,
Li Jiang,
Shu Xiaoming,
Zhang Lu,
Xu Yuan,
Li Xiaoya,
Zuo Jieyu,
Lv Cheng,
Kong Xiaomu,
Xiao Cheng
Publication year - 2019
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.1446
Subject(s) - odds ratio , methotrexate , single nucleotide polymorphism , rheumatoid arthritis , snp , medicine , pharmacology , adverse effect , confidence interval , arthritis , genotype , bioinformatics , genetics , gene , biology
Methotrexate (MTX) is a first‐line disease‐modifying antirheumatic drug for rheumatoid arthritis (RA), but individual variation in treatment response remains unexplained. The differences in drug efficacy and adverse drug reactions may be caused by genetic variations. We investigated the effects of single‐nucleotide polymorphisms (SNPs) in 2 genes encoding membrane‐spanning proteins, namely, reduced folate carrier‐1 RFC‐1/SLC19A1 (G>A [rs7499], A>G [rs2838956] and 180G>A [rs1051266]) and adenosine triphosphate–binding cassette B1 (rs1045642). Tagged SNPs were genotyped in 162 patients with RA in China. Then, we analyzed the relationships between these SNPs and therapeutic outcomes related to MTX in Chinese RA patients. No significant associations were found between the RFC‐1/SLC19A1 (G>A [rs7499] and A>G [rs2838956]) and adenosine triphosphate–binding cassette B1 (rs1045642) gene polymorphisms and the response to MTX in RA patients. However, MTX‐related toxicity was associated with one SNP, RFC‐1 rs1051266 AA vs GG (odds ratio, 6.523; 95% confidence interval, 1.596–26.565; P = .009). SLC19A1 A>G rs2838956 showed a trend toward a significant association (odds ratio, 0.377; 95% confidence interval, 0.124–1.143; P = .085) with toxicity. Our results suggest that the RFC‐1 80G>A (rs1051266) SNP exerts a potentially protective effect against the risk of adverse drug reactions in Chinese RA patients treated with MTX. Further studies are required to validate these findings.