类风湿关节炎滑膜细胞周期的基因调节

类风湿关节炎 (ｒｈｅｕｍａｔｏｉｄａｒｔｈｒｉｔｉｓ ,ＲＡ)是一种以滑膜衬里层细胞增生、血管翳形成、单个核细胞浸润 ,进而软骨侵蚀和关节破坏为特征的慢性炎症性疾病。目前 ,ＲＡ滑膜增生的确切机制尚不明确。有研究表明 ,ＲＡ滑膜成纤维细胞在细胞周期中增生异常活跃 ,呈肿瘤样增生 ,是造成软骨破坏的一个重要原因。因此 ,调节细胞周期以减轻滑膜增生具有重要的临床意义。1　ＲＡ和细胞周期哺乳动物细胞增生周期分为ＤＮＡ合成前期 (Ｇ1)、ＤＮＡ合成期 (Ｓ)、ＤＮＡ合成后期 (Ｇ2 )和有丝分裂期 (Ｍ)共 4个阶段。细胞分化由细胞周…     

类风湿关节炎的基因治疗

类风湿关节炎 (ｒｈｅｕｍａｔｏｉｄａｒｔｈｒｉｔｉｓ,ＲＡ)目前尚没有令人满意的治疗。传统的治疗药物 ,其作用缺乏特异性 ,可产生很多毒副作用。ＲＡ的现代生物治疗 ,能够针对特异性的靶分子 ,给ＲＡ治疗开拓了新的途径。但是 ,绝大部分生物治疗需要高度纯化的蛋白质 ,价格昂贵 ;而且蛋白质口服活性差 ,在体内又会很快被清除 ,需要反复注射 ;另外 ,它们不能选择性地到达靶组织[1] 。ＲＡ基因治疗至少在理论上有可能部分克服这些缺陷[2 ,3] 。1　ＲＡ基因治疗的候选分子基因治疗是指为了治疗目的 ,将新的遗传物质导入机体细胞的疗法[4 ]…     

氨基咪唑氨甲酰转移酶基因多态性在类风湿关节炎患者甲氨蝶呤治疗中的研究

目的 探讨类风湿关节炎(RA)患者氨基咪唑氨甲酰转移酶(ATIC)基因347C/G(rs2372536)单核苷酸多态性(SNP)与甲氨蝶呤(MTX)疗效和不良反应的相关性.方法 收集RA患者359例,分为单用MTX组、MTX联用其他改善病情药(DMARDs)组、非MTX的DMARDs组,于治疗前和治疗后12、24周检查患者临床及实验室指标,评价疗效(采用ACR20)及不良反应.采用实时荧光定量聚合酶链反应(PCR)法检测RA患者及340名健康对照组的ATIC基因C347G多态性,比较2组间基因型分布及等位基因频率.结果 RA与健康对照组ATIC基因347C/G基因型分布频率差异无统计学意义(P>0.05).单用MTX治疗组的有效率为72%(77/107例),有效组ATIC 347CC,CG,GG基因型与无效组间差异无统计学意义(P>0.05),不良反应发生率为32.7%,且携带ATIC G等位基因型患者的不良反应发生率(22.4%)明显高于CC基因型组(10.3%)(OR=2.67,95%可信区间为1.27～5.59),差异有统计学意义(P<0.05).MTX联用其他DMARDs(128例)组及非MTX的DMARDs组(90例),ATIC基因多态性与其疗效及不良反应无关(P>0.05).结论 ATIC基因347C/G多态性在RA患者与健康对照组间差异无统计学意义;与MTX治疗RA的疗效无明显相关性,但ATIC G等位基因与MTX的不良反应密切相关.因此ATIC基因347C/G多态性可能作为患者使用MTX的出现不良反应的预测指标.     

类风湿关节炎的诊断与治疗误区

类风湿关节炎(RA)是最常见的自身免疫性疾病之一，属于一种致残性疾病，在我国的患病率约为0．32％～0．36％。长期以来因其多发性和严重性而受到了较为广泛的关注，但迄今为止，RA仍然缺乏一个较为敏感而特异的诊断方法，也因此在其诊断和治疗过程中存在较多误诊和误治的现象，本文作者复习了相关文献后作如下总结：     

HLA-DR_4基因检测在类风湿关节炎诊治中的意义探讨

为了研究HLA-DR_4基因检测在类风湿关节炎诊治中的意义,对50例类风湿关节炎患者进行了HLA-DR_4的(PCR-SSP方法)检测,同时结合患者的临床表现和实验室指标进行分析。结果显示:HLA-DR_4阳性者31例(阳性率为62％);比较HLA-DR_4阳性和阴性两组患者其他指标,可见,HLA-DR_4阳性组的关节疼痛指数、ESR、类风湿因子(RF)滴度均明显高于HLA-DR_4阴性组(P值分别<0.05或0.01),手腕部X线在Ⅱ级～Ⅲ级异常变化者也以HLA-DR_4阳性组较多(P<0.005)。结果提示:HLA-DR_4基因检测是临床作为类风湿关节炎患者判断病情和估计预后有价值的指标之一,值得进一步探讨。     

氨基咪唑氨甲酰转移酶基因多态性在类风湿关节炎患者甲氨蝶呤治疗中的研究

Objective To investigate the relationship between the single nucleotide polymorphism of aminoimidazole carbexamide ribonucleotide transformylase gene and the efficacy and toxicity of methotrexate treatment in rheumatoid arthritis. Methods Total of 359 patients with RA were divided into mono-therapy with MTX group, combination therapy with other DMARDs group and other DMARDs combination with no MTX treatment group. The clinical and laboratory measurements were evaluated before therapy and 12, 24 weeks after therapy. Efficacy (evaluated by ACR20) and side effects of the drugs were also assessed. Real-time fluorescent quantitative PCR was conducted to test ATIC 347C/G mutation in RA patients and 340 healthy controls. Results There was no statistical significant difference in 347 CC, CG, GG between RA patients and healthy controls. In the MTX mono-therapy group (n=107), 72% (n=77) there was no statistical significant difference in 347CC, CG, GG between patients with good response and patients without efficacy. 32.7%(n=35) of these patients experienced adverse drug reactions. The ATIC G allele carriers (22.4%) experienced a greater frequency of side effects than the CC carriers (OR=2.672, 95%CI, 1.27～5.59, P<0.05). In MTX combined with other DMARDs group (n=128) and other DMARDs combination without MTX group (n=90), the polymorphism in the ATIC gene was not associated with good clinical response and adverse events (P>0.05). Conclusion There is no statistical significant difference between RA and healthy controls in the ATIC347 gene. Polymorphism in the ATIC gene is not associated with clinical response to MTX treatment, but the ATIC347 G allele is associated with MTX toxicity. It maybe used to predict the adverse drug reactions of patients who take MTX.     

氨基咪唑氨甲酰转移酶基因多态性在类风湿关节炎患者甲氨蝶呤治疗中的研究

Objective To investigate the relationship between the single nucleotide polymorphism of aminoimidazole carbexamide ribonucleotide transformylase gene and the efficacy and toxicity of methotrexate treatment in rheumatoid arthritis. Methods Total of 359 patients with RA were divided into mono-therapy with MTX group, combination therapy with other DMARDs group and other DMARDs combination with no MTX treatment group. The clinical and laboratory measurements were evaluated before therapy and 12, 24 weeks after therapy. Efficacy (evaluated by ACR20) and side effects of the drugs were also assessed. Real-time fluorescent quantitative PCR was conducted to test ATIC 347C/G mutation in RA patients and 340 healthy controls. Results There was no statistical significant difference in 347 CC, CG, GG between RA patients and healthy controls. In the MTX mono-therapy group (n=107), 72% (n=77) there was no statistical significant difference in 347CC, CG, GG between patients with good response and patients without efficacy. 32.7%(n=35) of these patients experienced adverse drug reactions. The ATIC G allele carriers (22.4%) experienced a greater frequency of side effects than the CC carriers (OR=2.672, 95%CI, 1.27～5.59, P<0.05). In MTX combined with other DMARDs group (n=128) and other DMARDs combination without MTX group (n=90), the polymorphism in the ATIC gene was not associated with good clinical response and adverse events (P>0.05). Conclusion There is no statistical significant difference between RA and healthy controls in the ATIC347 gene. Polymorphism in the ATIC gene is not associated with clinical response to MTX treatment, but the ATIC347 G allele is associated with MTX toxicity. It maybe used to predict the adverse drug reactions of patients who take MTX.     

氨基咪唑氨甲酰转移酶基因多态性在类风湿关节炎患者甲氨蝶呤治疗中的研究

Objective To investigate the relationship between the single nucleotide polymorphism of aminoimidazole carbexamide ribonucleotide transformylase gene and the efficacy and toxicity of methotrexate treatment in rheumatoid arthritis. Methods Total of 359 patients with RA were divided into mono-therapy with MTX group, combination therapy with other DMARDs group and other DMARDs combination with no MTX treatment group. The clinical and laboratory measurements were evaluated before therapy and 12, 24 weeks after therapy. Efficacy (evaluated by ACR20) and side effects of the drugs were also assessed. Real-time fluorescent quantitative PCR was conducted to test ATIC 347C/G mutation in RA patients and 340 healthy controls. Results There was no statistical significant difference in 347 CC, CG, GG between RA patients and healthy controls. In the MTX mono-therapy group (n=107), 72% (n=77) there was no statistical significant difference in 347CC, CG, GG between patients with good response and patients without efficacy. 32.7%(n=35) of these patients experienced adverse drug reactions. The ATIC G allele carriers (22.4%) experienced a greater frequency of side effects than the CC carriers (OR=2.672, 95%CI, 1.27～5.59, P<0.05). In MTX combined with other DMARDs group (n=128) and other DMARDs combination without MTX group (n=90), the polymorphism in the ATIC gene was not associated with good clinical response and adverse events (P>0.05). Conclusion There is no statistical significant difference between RA and healthy controls in the ATIC347 gene. Polymorphism in the ATIC gene is not associated with clinical response to MTX treatment, but the ATIC347 G allele is associated with MTX toxicity. It maybe used to predict the adverse drug reactions of patients who take MTX.     

山东地区类风湿关节炎与HLA-DRB1基因共同表位的关联性研究

目的　探讨山东地区汉族人群类风湿关节炎 (RA)与HLA DRB1基因共同表位 (SE)的关联性。方法　采用特异性引物聚合酶链反应 (PCR SSP)方法对山东地区人群 1 32例RA患者及1 30名正常健康者的HLA DRB1 0 1、 0 4、 1 0的 1 7个等位基因进行检测。结果　山东地区RA患者中携带有SE的基因频率显著高于正常对照组 (5 0 0 %∶2 2 3% ,P <0 0 1 ) ,HLA DR4亚型 0 4 0 5是主要的易感基因 (2 2 8%∶1 0 0 % ,P <0 0 0 5 )。其他亚型包括DRB1 0 1 0 1 (3 8%∶3 1 % ) , 0 1 0 2 (2 3%∶2 3% ) , 0 1 0 3(3 8%∶3 1 % ) , 0 1 0 4 (3 0 %∶2 3% ) , 0 4 0 1 (1 0 6 %∶4 6 % ) , 0 4 0 4 (9 1 %∶4 6 % ) , 0 4 0 7(8 3%∶9 2 % ) , 0 4 0 3(6 8%∶3 1 % ) , 0 4 0 2 (6 8%∶4 6 % ) , 0 4 0 8(5 3%∶1 5 % ) , 0 4 0 9(2 3%∶0 ) , 0 4 0 6 (1 5 %∶0 ) , 0 4 1 0 (0 8%∶0 ) , 0 4 1 1 (0 8%∶0 )和 1 0 0 1 (1 1 4 %∶6 9% )的差别均无统计学意义。Logistic回归分析表明 :SE纯合子对RA的危害性要比其杂合子大 (P <0 0 0 1 )。结论　SE与山东地区汉族RA易感性及疾病严重性有关联     

雌激素受体基因多态性与女性类风湿关节炎相关性的研究

目的分析雌激素受体(ER)基因XbaⅠ和PvuⅡ酶切多态性在女性类风湿关节炎(RA)中的分布,探讨其与人类白细胞抗原(HLA)-DRβ1*04基因亚型、类风湿因子(RF)以及RA患者临床表现的关系。方法采用聚合酶链反应-限制性片断长度多态性(PCR-RFLP)技术,对81例女性RA患者和146名女性正常对照者的ER基因(XbaⅠ、PvuⅡ位点)进行分型,并计算基因分布频率。分析患者的HLA-DRβ1*04基因亚型、RF以及临床表现与ER基因多态性之间的关系。结果女性RA患者的ER基因X、P基因频率均明显高于健康对照组,ER基因的XX和PP基因亚型的阳性率分别高于正常对照组(P<0.05)。而RA患者的xx基因亚型的阳性率明显低于健康对照组(P<0.05)。RA患者XXPP基因型的阳性率明显高于健康对照组,而xxpp基因型的阳性率明显低于健康对照组(P<0.05)。携带PP基因型的RA患者HLA-DRβ1*04基因亚型的阳性率明显升高(P<0.05)。ER基因中pp基因型、XXpp和xxPP基因型的患者关节受累数明显增高(P<0.05)。结论女性RA患者ER基因的X和P的基因频率表达明显增高。ER基因酶切多态性分析中,XX、PP及XXPP基因型可能与女性RA的易感性相关。PP基因型可能与HLA-DRβ1*04基因有一定的相关性,pp基因型、XXpp和xxPP基因型可能与RA关节病变的程度相关。     

氨基咪唑氨甲酰转移酶基因多态性在类风湿关节炎患者甲氨蝶呤治疗中的研究

Objective To investigate the relationship between the single nucleotide polymorphism of aminoimidazole carbexamide ribonucleotide transformylase gene and the efficacy and toxicity of methotrexate treatment in rheumatoid arthritis. Methods Total of 359 patients with RA were divided into mono-therapy with MTX group, combination therapy with other DMARDs group and other DMARDs combination with no MTX treatment group. The clinical and laboratory measurements were evaluated before therapy and 12, 24 weeks after therapy. Efficacy (evaluated by ACR20) and side effects of the drugs were also assessed. Real-time fluorescent quantitative PCR was conducted to test ATIC 347C/G mutation in RA patients and 340 healthy controls. Results There was no statistical significant difference in 347 CC, CG, GG between RA patients and healthy controls. In the MTX mono-therapy group (n=107), 72% (n=77) there was no statistical significant difference in 347CC, CG, GG between patients with good response and patients without efficacy. 32.7%(n=35) of these patients experienced adverse drug reactions. The ATIC G allele carriers (22.4%) experienced a greater frequency of side effects than the CC carriers (OR=2.672, 95%CI, 1.27～5.59, P<0.05). In MTX combined with other DMARDs group (n=128) and other DMARDs combination without MTX group (n=90), the polymorphism in the ATIC gene was not associated with good clinical response and adverse events (P>0.05). Conclusion There is no statistical significant difference between RA and healthy controls in the ATIC347 gene. Polymorphism in the ATIC gene is not associated with clinical response to MTX treatment, but the ATIC347 G allele is associated with MTX toxicity. It maybe used to predict the adverse drug reactions of patients who take MTX.     

氨基咪唑氨甲酰转移酶基因多态性在类风湿关节炎患者甲氨蝶呤治疗中的研究

Objective To investigate the relationship between the single nucleotide polymorphism of aminoimidazole carbexamide ribonucleotide transformylase gene and the efficacy and toxicity of methotrexate treatment in rheumatoid arthritis. Methods Total of 359 patients with RA were divided into mono-therapy with MTX group, combination therapy with other DMARDs group and other DMARDs combination with no MTX treatment group. The clinical and laboratory measurements were evaluated before therapy and 12, 24 weeks after therapy. Efficacy (evaluated by ACR20) and side effects of the drugs were also assessed. Real-time fluorescent quantitative PCR was conducted to test ATIC 347C/G mutation in RA patients and 340 healthy controls. Results There was no statistical significant difference in 347 CC, CG, GG between RA patients and healthy controls. In the MTX mono-therapy group (n=107), 72% (n=77) there was no statistical significant difference in 347CC, CG, GG between patients with good response and patients without efficacy. 32.7%(n=35) of these patients experienced adverse drug reactions. The ATIC G allele carriers (22.4%) experienced a greater frequency of side effects than the CC carriers (OR=2.672, 95%CI, 1.27～5.59, P<0.05). In MTX combined with other DMARDs group (n=128) and other DMARDs combination without MTX group (n=90), the polymorphism in the ATIC gene was not associated with good clinical response and adverse events (P>0.05). Conclusion There is no statistical significant difference between RA and healthy controls in the ATIC347 gene. Polymorphism in the ATIC gene is not associated with clinical response to MTX treatment, but the ATIC347 G allele is associated with MTX toxicity. It maybe used to predict the adverse drug reactions of patients who take MTX.     

氨基咪唑氨甲酰转移酶基因多态性在类风湿关节炎患者甲氨蝶呤治疗中的研究

Objective To investigate the relationship between the single nucleotide polymorphism of aminoimidazole carbexamide ribonucleotide transformylase gene and the efficacy and toxicity of methotrexate treatment in rheumatoid arthritis. Methods Total of 359 patients with RA were divided into mono-therapy with MTX group, combination therapy with other DMARDs group and other DMARDs combination with no MTX treatment group. The clinical and laboratory measurements were evaluated before therapy and 12, 24 weeks after therapy. Efficacy (evaluated by ACR20) and side effects of the drugs were also assessed. Real-time fluorescent quantitative PCR was conducted to test ATIC 347C/G mutation in RA patients and 340 healthy controls. Results There was no statistical significant difference in 347 CC, CG, GG between RA patients and healthy controls. In the MTX mono-therapy group (n=107), 72% (n=77) there was no statistical significant difference in 347CC, CG, GG between patients with good response and patients without efficacy. 32.7%(n=35) of these patients experienced adverse drug reactions. The ATIC G allele carriers (22.4%) experienced a greater frequency of side effects than the CC carriers (OR=2.672, 95%CI, 1.27～5.59, P<0.05). In MTX combined with other DMARDs group (n=128) and other DMARDs combination without MTX group (n=90), the polymorphism in the ATIC gene was not associated with good clinical response and adverse events (P>0.05). Conclusion There is no statistical significant difference between RA and healthy controls in the ATIC347 gene. Polymorphism in the ATIC gene is not associated with clinical response to MTX treatment, but the ATIC347 G allele is associated with MTX toxicity. It maybe used to predict the adverse drug reactions of patients who take MTX.     

氨基咪唑氨甲酰转移酶基因多态性在类风湿关节炎患者甲氨蝶呤治疗中的研究

Objective To investigate the relationship between the single nucleotide polymorphism of aminoimidazole carbexamide ribonucleotide transformylase gene and the efficacy and toxicity of methotrexate treatment in rheumatoid arthritis. Methods Total of 359 patients with RA were divided into mono-therapy with MTX group, combination therapy with other DMARDs group and other DMARDs combination with no MTX treatment group. The clinical and laboratory measurements were evaluated before therapy and 12, 24 weeks after therapy. Efficacy (evaluated by ACR20) and side effects of the drugs were also assessed. Real-time fluorescent quantitative PCR was conducted to test ATIC 347C/G mutation in RA patients and 340 healthy controls. Results There was no statistical significant difference in 347 CC, CG, GG between RA patients and healthy controls. In the MTX mono-therapy group (n=107), 72% (n=77) there was no statistical significant difference in 347CC, CG, GG between patients with good response and patients without efficacy. 32.7%(n=35) of these patients experienced adverse drug reactions. The ATIC G allele carriers (22.4%) experienced a greater frequency of side effects than the CC carriers (OR=2.672, 95%CI, 1.27～5.59, P<0.05). In MTX combined with other DMARDs group (n=128) and other DMARDs combination without MTX group (n=90), the polymorphism in the ATIC gene was not associated with good clinical response and adverse events (P>0.05). Conclusion There is no statistical significant difference between RA and healthy controls in the ATIC347 gene. Polymorphism in the ATIC gene is not associated with clinical response to MTX treatment, but the ATIC347 G allele is associated with MTX toxicity. It maybe used to predict the adverse drug reactions of patients who take MTX.     

氨基咪唑氨甲酰转移酶基因多态性在类风湿关节炎患者甲氨蝶呤治疗中的研究

Objective To investigate the relationship between the single nucleotide polymorphism of aminoimidazole carbexamide ribonucleotide transformylase gene and the efficacy and toxicity of methotrexate treatment in rheumatoid arthritis. Methods Total of 359 patients with RA were divided into mono-therapy with MTX group, combination therapy with other DMARDs group and other DMARDs combination with no MTX treatment group. The clinical and laboratory measurements were evaluated before therapy and 12, 24 weeks after therapy. Efficacy (evaluated by ACR20) and side effects of the drugs were also assessed. Real-time fluorescent quantitative PCR was conducted to test ATIC 347C/G mutation in RA patients and 340 healthy controls. Results There was no statistical significant difference in 347 CC, CG, GG between RA patients and healthy controls. In the MTX mono-therapy group (n=107), 72% (n=77) there was no statistical significant difference in 347CC, CG, GG between patients with good response and patients without efficacy. 32.7%(n=35) of these patients experienced adverse drug reactions. The ATIC G allele carriers (22.4%) experienced a greater frequency of side effects than the CC carriers (OR=2.672, 95%CI, 1.27～5.59, P<0.05). In MTX combined with other DMARDs group (n=128) and other DMARDs combination without MTX group (n=90), the polymorphism in the ATIC gene was not associated with good clinical response and adverse events (P>0.05). Conclusion There is no statistical significant difference between RA and healthy controls in the ATIC347 gene. Polymorphism in the ATIC gene is not associated with clinical response to MTX treatment, but the ATIC347 G allele is associated with MTX toxicity. It maybe used to predict the adverse drug reactions of patients who take MTX.     

氨基咪唑氨甲酰转移酶基因多态性在类风湿关节炎患者甲氨蝶呤治疗中的研究

Objective To investigate the relationship between the single nucleotide polymorphism of aminoimidazole carbexamide ribonucleotide transformylase gene and the efficacy and toxicity of methotrexate treatment in rheumatoid arthritis. Methods Total of 359 patients with RA were divided into mono-therapy with MTX group, combination therapy with other DMARDs group and other DMARDs combination with no MTX treatment group. The clinical and laboratory measurements were evaluated before therapy and 12, 24 weeks after therapy. Efficacy (evaluated by ACR20) and side effects of the drugs were also assessed. Real-time fluorescent quantitative PCR was conducted to test ATIC 347C/G mutation in RA patients and 340 healthy controls. Results There was no statistical significant difference in 347 CC, CG, GG between RA patients and healthy controls. In the MTX mono-therapy group (n=107), 72% (n=77) there was no statistical significant difference in 347CC, CG, GG between patients with good response and patients without efficacy. 32.7%(n=35) of these patients experienced adverse drug reactions. The ATIC G allele carriers (22.4%) experienced a greater frequency of side effects than the CC carriers (OR=2.672, 95%CI, 1.27～5.59, P<0.05). In MTX combined with other DMARDs group (n=128) and other DMARDs combination without MTX group (n=90), the polymorphism in the ATIC gene was not associated with good clinical response and adverse events (P>0.05). Conclusion There is no statistical significant difference between RA and healthy controls in the ATIC347 gene. Polymorphism in the ATIC gene is not associated with clinical response to MTX treatment, but the ATIC347 G allele is associated with MTX toxicity. It maybe used to predict the adverse drug reactions of patients who take MTX.     

氨基咪唑氨甲酰转移酶基因多态性在类风湿关节炎患者甲氨蝶呤治疗中的研究

Objective To investigate the relationship between the single nucleotide polymorphism of aminoimidazole carbexamide ribonucleotide transformylase gene and the efficacy and toxicity of methotrexate treatment in rheumatoid arthritis. Methods Total of 359 patients with RA were divided into mono-therapy with MTX group, combination therapy with other DMARDs group and other DMARDs combination with no MTX treatment group. The clinical and laboratory measurements were evaluated before therapy and 12, 24 weeks after therapy. Efficacy (evaluated by ACR20) and side effects of the drugs were also assessed. Real-time fluorescent quantitative PCR was conducted to test ATIC 347C/G mutation in RA patients and 340 healthy controls. Results There was no statistical significant difference in 347 CC, CG, GG between RA patients and healthy controls. In the MTX mono-therapy group (n=107), 72% (n=77) there was no statistical significant difference in 347CC, CG, GG between patients with good response and patients without efficacy. 32.7%(n=35) of these patients experienced adverse drug reactions. The ATIC G allele carriers (22.4%) experienced a greater frequency of side effects than the CC carriers (OR=2.672, 95%CI, 1.27～5.59, P<0.05). In MTX combined with other DMARDs group (n=128) and other DMARDs combination without MTX group (n=90), the polymorphism in the ATIC gene was not associated with good clinical response and adverse events (P>0.05). Conclusion There is no statistical significant difference between RA and healthy controls in the ATIC347 gene. Polymorphism in the ATIC gene is not associated with clinical response to MTX treatment, but the ATIC347 G allele is associated with MTX toxicity. It maybe used to predict the adverse drug reactions of patients who take MTX.