Genetic polymorphisms in key methotrexate pathway genes are associated with response to treatment in rheumatoid arthritis patients

被引：97
|
作者：
Owen, S. A. [1 ]
Hider, S. L. [2 ]
Martin, P. [1 ]
Bruce, I. N. [1 ]
Barton, A. [1 ]
Thomson, W. [1 ]
机构：
[1] Univ Manchester, Arthrit Res UK Epidemiol Unit, Manchester Acad Hlth Sci Ctr, Manchester M13 9PT, Lancs, England
[2] Keele Univ, Natl Primary Care Ctr, Arthrit Res UK, Keele, Staffs, England
来源：
PHARMACOGENOMICS JOURNAL | 2013年 / 13卷 / 03期
关键词：
ATIC; methotrexate; pharmacogenetics; polymorphism; RFC; rheumatoid arthritis; REDUCED FOLATE CARRIER; LOW-DOSE METHOTREXATE; THYMIDYLATE-SYNTHASE; COMMON POLYMORPHISMS; METHYLENETETRAHYDROFOLATE REDUCTASE; RIBONUCLEOTIDE TRANSFORMYLASE; ANTIRHEUMATIC DRUG; EFFICACY; TOXICITY; THERAPY;
D O I：
10.1038/tpj.2012.7
中图分类号：
Q3 [遗传学];
学科分类号：
071007 ; 090102 ;
摘要：
We investigated the effect of single-nucleotide polymorphisms (SNPs) spanning 10 methotrexate (MTX) pathway genes, namely AMPD1, ATIC, DHFR, FPGS, GGH, ITPA, MTHFD1, SHMT1, SLC19A1 (RFC) and TYMS on the outcome of MTX treatment in a UK rheumatoid arthritis (RA) patient cohort. Tagging SNPs were selected and genotyping was performed in 309 patients with predefined outcomes to MTX treatment. Of the 129 SNPs tested, 11 associations were detected with efficacy (P-trend <= 0.05) including four SNPs in the ATIC gene (rs12995526, rs3821353, rs7563206 and rs16853834), six SNPs in the SLC19A1 gene region (rs11702425, rs2838956, rs7499, rs2274808, rs9977268 and rs7279445) and a single SNP within the GGH gene (rs12681874). Five SNPs were significantly associated with adverse events; three in the DHFR gene (rs12517451, rs10072026, and rs1643657) and two of borderline significance in the FPGS gene. The results suggest that genetic variations in several key MTX pathway genes may influence response to MTX in the RA patients. Further studies will be required to validate these findings and if confirmed these results could contribute towards a better understanding of and ability to predict MTX response in RA.
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收藏
页码：227 / 234
页数：8
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