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首页> 外文期刊>Pharmacogenomics >Moving toward personalized medicine in rheumatoid arthritis: SNPs in methotrexate intracellular pathways are associated with methotrexate therapeutic outcome
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Moving toward personalized medicine in rheumatoid arthritis: SNPs in methotrexate intracellular pathways are associated with methotrexate therapeutic outcome

机译：向类风湿关节炎的个性化医学迈进：甲氨蝶呤细胞内途径中的SNP与甲氨蝶呤的治疗结果相关

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Aim: Evaluate the potential of selected SNPs as predictors of methotrexate (MTX) therapeutic outcome. Patients & methods: In total, 35 SNPs in 14 genes involved in MTX intracellular pathways and Phase II reactions were genotyped in 233 rheumatoid arthritis (RA) patients treated with MTX. Binary logistic regressions were performed by genotype/haplotype-based approaches. Non-Response-and Toxicity-Genetic Risk Indexes (Non-RespGRI and ToxGRI) were created. Results: MTX nonresponse was associated to eight genotypes and three haplotypes: MTHFR rs1801131 AA and rs1801133 TT; MS rs1805087 AA; MTRR rs1801394 A carriers; ATIC rs2372536 C carriers, rs4673993 T carriers, rs7563206 T carriers and rs12995526 T carriers; CC for GGH rs3758149 and rs12681874; CGTTT for ATIC combination 1; and CTTTC for ATIC combination 2. From overall Non-RespGRI patients with indexes 6-8 had more than sixfold increased risk for MTX nonresponse than those patients with indexes 0-5. MTX-related toxicity was associated to five genotypes and two haplotypes: ATIC rs2372536 G carriers, rs3821353 T carriers, rs7563206 CC and rs12995526 CC; ADORA2A rs2267076 T; CTTCC for ATIC combination 1; and TC for ADORA2A rs2267076 and rs2298383. From overall ToxGRI, patients with indexes 3-4 had more than sevenfold increased risk for MTX-related toxicity than those patients with indexes 1-2. Conclusion: Genotyping may be helpful to identify which RA patients will not benefit from MTX treatment and, consequently, important to personalized medicine in RA. Nevertheless, further studies are required to validate these findings.
机译：目的：评估选定的SNP作为甲氨蝶呤（MTX）治疗结果的预测指标的潜力。患者与方法：在233例接受MTX治疗的类风湿性关节炎（RA）患者中，总共对涉及MTX细胞内途径和II期反应的14个基因中的35个SNP进行了基因分型。通过基于基因型/单倍型的方法进行二元逻辑回归。创建了无反应和毒性遗传风险指数（Non-RespGRI和ToxGRI）。结果：MTX无应答与八种基因型和三种单倍型相关：MTHFR rs1801131 AA和rs1801133 TT; MS rs1805087 AA; MTRR rs1801394 A载波; ATIC rs2372536 C载体，rs4673993 T载体，rs7563206 T载体和rs12995526 T载体; GGH rs3758149和rs12681874的CC; ATIC组合1的CGTTT;和ATT联合用CTTTC2。总的来说，指数为6-8的Non-RespGRI患者的MTX无反应风险比指数为0-5的患者高六倍。与MTX相关的毒性与五种基因型和两种单倍型相关：ATIC rs2372536 G携带者，rs3821353 T携带者，rs7563206 CC和rs12995526 CC; ADORA2A rs2267076 T; ATIC组合1的CTTCC;和ADORA2A rs2267076和rs2298383的TC。从总体ToxGRI来看，指标3-4的患者发生MTX相关毒性的风险比指标1-2的患者高7倍以上。结论：基因分型可能有助于确定哪些RA患者不能从MTX治疗中受益，因此，对于RA的个性化医学很重要。然而，需要进一步的研究来验证这些发现。

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