Lee Young Ho, Bae Sang-Cheol
Division of Rheumatology, Department of Internal Medicine, Korea University College of Medicine, Korea University Anam Hospital, 73, Inchon-ro, Seongbuk-gu, Seoul, Korea.
Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea.
Rheumatol Int. 2016 Nov;36(11):1591-1599. doi: 10.1007/s00296-016-3523-2. Epub 2016 Jul 5.
This study investigated whether the 5-aminoimidazole-4-carboxamide ribonucleotide transformylase gene (ATIC) 347 C/G polymorphism can predict the response to or toxicity of methotrexate (MTX) in patients with rheumatoid arthritis (RA). We conducted a meta-analysis of studies on the association between ATIC 347 C/G polymorphism and non-responsiveness to or toxicity of MTX in RA patients, using PUBMED, EMBASE, and COCHRANE. Nine comparative studies from 6 articles including 1056 RA patients met our inclusion criteria. This final group of studies comprised 5 studies on response to MTX and 4 on toxicity of MTX in RA patients in relation to the ATIC 347 C/G polymorphism status. Meta-analysis showed association between the ATIC 347 GG + GC genotype and non-response to MTX therapy (OR = 1.572, 95 % CI 1.146-2.156, p = 0.005). Stratification by ethnicity indicated significant association between the ATIC 347 GG + GC genotype and non-response to MTX in Caucasians (OR = 1.884, 95 % CI 1.236-2.873, p = 0.003), but not in Asian patients. Similarly, associations were noted for the ATIC 347 C/G polymorphism through analysis using recessive and overdominant models. Meta-analysis revealed association between the ATIC 347 GG + GC genotype and MTX toxicity (OR = 1.454 95 % CI 1.034-2.044, p = 0.032). Stratification by ethnicity indicated significant association between the ATIC 347 GG + GC genotype and MTX toxicity in Caucasians (OR = 1.741, 95 % CI 1.080-2.806, p = 0.023), but not in Asian patients. The ATIC 347 C/G polymorphism may be associated with non-responsiveness to and or toxicity of MTX in Caucasian RA patients.
本研究调查了5-氨基咪唑-4-甲酰胺核糖核苷酸转甲酰酶基因（ATIC）347 C/G多态性是否能够预测类风湿关节炎（RA）患者对甲氨蝶呤（MTX）的反应或毒性。我们使用PUBMED、EMBASE和COCHRANE对ATIC 347 C/G多态性与RA患者对MTX无反应或毒性之间关联的研究进行了荟萃分析。来自6篇文章的9项比较研究纳入了1056例RA患者，符合我们的纳入标准。这组最终研究包括5项关于RA患者对MTX反应的研究和4项关于RA患者中ATIC 347 C/G多态性状态与MTX毒性关系的研究。荟萃分析显示ATIC 347 GG + GC基因型与对MTX治疗无反应之间存在关联（OR = 1.572，95% CI 1.146 - 2.156，p = 0.005）。按种族分层表明，ATIC 347 GG + GC基因型与白种人对MTX无反应之间存在显著关联（OR = 1.884，95% CI 1.236 - 2.873，p = 0.003），但在亚洲患者中无此关联。同样，通过隐性和超显性模型分析，ATIC 347 C/G多态性也存在关联。荟萃分析显示ATIC 347 GG + GC基因型与MTX毒性之间存在关联（OR = 1.454，95% CI 1.034 - 2.044，p = 0.032）。按种族分层表明，ATIC 347 GG + GC基因型与白种人MTX毒性之间存在显著关联（OR = 1.741，95% CI 1.080 - 2.806，p = 0.023），但在亚洲患者中无此关联。ATIC 347 C/G多态性可能与白种人RA患者对MTX无反应和/或毒性有关。
