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目的考察多药耐药基因MDR1的单核苷酸多态性(SNP)C1236T与炎症性肠病(IBD)患者服用硫嘌呤类药物后的活性代谢产物6-硫鸟苷酸(6-TGNs)的相关性。方法有105名患者纳入研究,收集全血提取DNA,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)法,进行MDR1C1236T基因型分析,采用HPLC方法检测红细胞内6-TGNs的浓度,并统计药物不良反应情况。卡方检验分析相关性。结果相同剂量下,6-TGNs浓度在1236CT/TT型携带者比CC型携带者高(P=0.048);同时,1236CT/TT型携带者服药后发生不良反应的风险显著高于1236CC型携带者(P=0.045)。结论 MDR1 1236 C>T突变与高6-TGNs浓度及高不良反应发生率密切相关。
Objective To investigate the effects of 6-thioguanosine (6-TGNs), an active metabolite of thiopurines, on the single nucleotide polymorphisms (SNPs) of multidrug resistance gene MDR1 and the patients with inflammatory bowel disease (IBD) Relevance. Methods A total of 105 patients were included in the study. DNA was extracted from whole blood. The genotypes of MDR1C1236T were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The levels of 6-TGNs in erythrocytes Concentration, and statistics of adverse drug reactions. Chi-square test analysis of relevance. Results At the same dose, the 6-TGNs concentration was higher in carriers of type 1236CT / TT than those in carriers of type CC (P = 0.048). Meanwhile, the risk of adverse reactions in 1236CT / TT carriers was significantly higher than that in carriers of type 1236CC (P = 0.045). Conclusion The MDR1 1236 C> T mutation is closely related to the concentration of high 6-TGNs and the incidence of high adverse reactions.