人类DHODH 19C>A基因多态性对来氟米特治疗类风湿关节炎临床疗效影响  

Investigation of the DHODH Genetic Polymorphism( 19C > A ) Response to Leflunomide Treatment in Rheumatoid Arthritis

作　　者：杨群智 张舸[1] 和晶[1] Yang Qunzhi, Zhang Ge, He Jing.(Department of Rheumatology and Immunology, Beijing Haidian Hospital ,Beijing 100080, Chin)

机构地区：[1]北京市海淀医院、北京大学第三医院海淀院区风湿免疫科,100080

出　　处：《医学研究杂志》2018年第3期134-137,共4页Journal of Medical Research

摘　　要：目的来氟米特(LEF)是一种改善病情的抗风湿药物(DMARDs)。其代谢产物A771726具有抑制二氢乳清酸脱氢酶(dihydroorotate dehydrogenase,DHODH)的作用,本研究目的是观察DHODH(rs3213422)19C>A基因多态性对LEF治疗类风湿关节炎(RA)疗效的影响。方法本研究包括105例RA患者,口服来氟米特20mg/d治疗。3个月及6个月后,评价患者是否达到ACR20及ACR50缓解标准。并行DHODH(rs3213422)19C>A基因多态性检测,观察不同基因类型患者病情改善情况。结果 LEF治疗RA,3个月时ACR20总体缓解率:C等位基因为70.0%,A等位基因为51.7%,两者比较差异有统计学意义(P=0.012);ACR50总体缓解率:C等位基因为38.0%,A等位基因为28.3%,两者比较差异无统计学意义(P=0.185)。治疗6个月时,ACR20总体缓解率:C等位基因为84.7%,A等位基因为61.7%。两者比较差异有统计学意义(P=0.006);ACR50总体缓解率:C等位基因为60.7%,A等位基因率为38.3%,两者比较差异有统计学意义(P=0.039)。结论 LEF治疗RA患者ACR20及ACR50缓解率,随治疗时间的延长而增加。DHODH(19C>A)的基因多态性与LEF治疗RA的临床疗效有一定相关性。携带C等位基因的患者应用LEF治疗的效果优于携带A等位基因的患者,两者之间的差异随治疗时间的延长逐渐增加。Objective Purpose leflunomide （LEF） is a disease-modifying antirheumatic drug used for treating rheumatoid arthritis （RA）. It is a prodrug that is rapidly converted in vivo to the active metabolite A77 1726.The mechanism of action of A77 1726 primarily involves inhibition of the enzyme DHODH. Related studies have found that DHOD gene has polymorphism. The aim of this study was to investigate whether genetic polymorphisms in DHODH（19C〉A） influence leflunomide pharmacokinetics and treatment response. Methods We studied 105 patients diagnosed with RA and treated with LEF （20 mg daily）. Follow-up was 6 months. Clinical improvement was valuated according to the American College of Rheumatology 20% and 50% response criteria. The peripheral blood genomic DNA was extracted, and amplified by PCR, analyzed by direct sequencing. The gene detection was performed in our hospital 105 patients with DHODH polymorphism（19C〉A）. Results After 3 months of therapy, the ACR20 criteria was met by 70.0% in C allele,51.7% in A allele. Differences were statistically significant（P=0.012）. The ACR50 criteria was met by 38.0% in C allele,28.3% in A allele. It did not reach statistically significant（P=0.185）.After 6 months of therapy, the ACR20 criteria was met by 84.7% in C allele,61.7% in A allele. Differences were statistically significant（P=0.006）. The ACR50 criteria was met by 60.7% in C allele,38.3% in A allele. Differences were statistically significant（P=0.039）. Conclusion The remission rate of ACR20 and ACR50 in patients with rheumatoid arthritis was increased with the treatment time. The results of the study suggest that DHODH（19C〉A） polymorphism may be associated with LEF treatment outcome in RA patients. Treatment response is better in the patients with the C allele than A allele. This trend is more obvious with the extension of time.

关 键 词：基因多态性 来氟米特 二氢乳清酸脱氢酶 

分 类 号：R5[医药卫生—内科学]