CYP3A5和MDR1基因多态性对沙格列汀疗效的影响

Influence of genetic polymorphisms in CYP3A5 and MDR1 on the efficacy of saxagliptin

目的:探讨P450酶CYP3A5和P-糖蛋白MDR1基因多态性对沙格列汀降糖疗效的影响。方法:98例2型糖尿病患者及84例健康对照抽取静脉血并提取DNA,用PCR-RFLP方法进行CYP3A5和MDR1基因分型。患者均口服二甲双胍8周后加用沙格列汀继续8周治疗,测定沙格列汀用药前后的空腹血糖、餐后血糖、糖化血红蛋白等临床指标。运用SPSS软件结合临床资料进行统计分析。结果:CYP3A5与MDR1各基因型的一般情况如年龄、性别、体重指数、腰臀比、空腹血糖、餐后血糖等均无统计学差异(P均>0.05)。二甲双胍和沙格列汀8周治疗后比较治疗前后不同基因型临床指标的差异发现:CYP3A5*3/*3基因型患者的空腹血糖、餐后血糖、餐后血清胰岛素、空腹血清胰岛素、糖化血红蛋白在用药前后改变显著大于CYP3A5*1/*1和*1/*3基因型患者(P均<0.05)。MDR1C3435T多态性CC基因型患者空腹血糖、餐后血糖、餐后血清胰岛素、胰岛素抵抗稳态模型评估糖化血红蛋白在用药前后改变显著大于MDR1C3435T的CT和TT基因型患者(P均<0.05)。结论:CYP3A5*1、*3基因型与MDR1 C3435T多态性能够影响2型糖尿病患者沙格列汀降糖疗效。其中,CYP3A5*3/*3基因型与MDR1C3435T CC基因型患者降糖疗效更好。

AIM： To investigate the influence of genetic polymorphisms in CYP3A5 and MDR1 on the efficacy of saxagliptin. METHODS： Blood and DNA of 98 type 2 diabetes mellitus patients and 84 healthy controls were extracted to genotype the CYP3A5 and MDR1 gene by PCR-RFLP method.Patients were treated with metformin for 8 weeks,then saxagliptin were added to continue the treatment for another 8 weeks. Clinical parameters such as body mass index（ BMI）,fasting plasma glucose（ FPG）,postprandial plasma glucose（ PPG）,glycated hemoglobin（ Hbalc）,fasting serum insulin（ FINS）,postprandial serum insulin（ PINS）,homeostasis model assessment for insulin resistance（ HOMA-IR） were collected before and after saxagliptin treatment. SPSS was used to analyze the data. RESULTS： No significant difference of age,gender,BMI,waist buttock ratio,FPG,PPG among different CYP3A5 and MDR1 genotpyes were detected（ All P 〉0. 05）. Changes before and after 8 weeks treatment of saxagliptin according to different CYP3A5 and MDR1genotypes were collected as the changes of FPG,PPG,FINS,PINS and Hb Alc in CYP3A5＊3 /＊3 genotype patients were found higher than those in CYP3A5＊1 /＊1 and＊1 /＊3 patients（ All P 0. 05）. FPG,PPG,PINS,HOMA-IR and Hbalc in MDR1 C3435 T CC genotypic patients were higher than those in CT and TT genotypic patients（ All P 0. 05）. CONCLUSION： CYP3A5＊1 and CYP3A5＊3 genotypes and MDR1 C3435 T polymorphisms can influence the hypoglycemic effect of saxagliptin in type 2 diabetes mellitus. CYP3A5＊3 /＊3genotypic patients and MDR1 C3435 T CC genotypic patients can receive better hypoglycemic efficacy.