论文部分内容阅读
目的探讨相关基因多态性和非遗传因素对甲氨蝶呤治疗强直性脊柱炎的疗效和毒性的影响,为个体化用药提供依据。方法选择105例于2009年12月~2015年1月在某院风湿科就诊的强直性脊柱炎患者。采用限制性片段长度多态性聚合酶链式反应法检测6个单核苷酸基因多态性位点,包括RFC1 G80A、MDR1 C3435T、GGH C-401T、FPGS(rs1544105)G>A、MTHFR C677T和MTHFR A1298C。采用χ~2检验、非参数检验、回归分析等方法检验上述基因及非遗传因素与甲氨蝶呤疗效及毒性间的相关性。结果年龄对强直性脊柱炎功能指数、疾病活动指数(BASFIb、BASDAIb)有显著影响(P=0.027,P=0.004),年龄越大,疗效越差(r=-0.216,r=-0.276)。MTHFR A1298C与总疗效有显著相关性(P=0.017),纯合型的患者更容易发生治疗失败。MDR1 C3435T纯合型对BASFIb有影响,纯合型患者躯体功能恢复更差(P=0.046)。各基因型与不良反应间的相关性差异无统计学意义。结论 MTHFR A1298C、MDR1 C3435T及年龄显著影响疗效,需注意个体化给药。暂未发现甲氨蝶呤不良反应的风险基因。
Objective To investigate the effects of genetic polymorphisms and non-genetic factors on the efficacy and toxicity of methotrexate in the treatment of ankylosing spondylitis, and to provide basis for individualized medication. Methods 105 cases of ankylosing spondylitis were treated in rheumatology department of a hospital from December 2009 to January 2015. Six SNPs were detected by restriction fragment length polymorphism polymerase chain reaction (PCR), including RFC1 G80A, MDR1 C3435T, GGH C-401T, FPGS (rs1544105) G> A, MTHFR C677T And MTHFR A1298C. Χ ~ 2 test, nonparametric test, regression analysis and other methods to test the above-mentioned gene and non-genetic factors and the efficacy and toxicity of methotrexate between the correlation. Results The age had significant effect on functional index of ankylosing spondylitis and disease activity index (BASFIb, BASDAIb) (P = 0.027, P = 0.004). The older the age, the poorer the efficacy (r = -0.216, r = -0.276). MTHFR A1298C was significantly associated with overall efficacy (P = 0.017), and homozygous patients were more likely to fail treatment. MDR1 C3435T homozygote had an effect on BASFIb, and homozygous patients had worse physical function recovery (P = 0.046). There was no significant difference between the genotypes and the adverse reactions. Conclusion MTHFR A1298C, MDR1 C3435T and age significantly affect the efficacy, attention should be paid to individualized administration. Yet found no risk of adverse reactions to methotrexate gene.