KCNJ11 rs5219基因多态性对新发2型糖尿病患者二甲双胍及格列齐特联用疗效的研究

Study of KCNJ11 rs5219 Gene Polymorphism on the Efficacy of Metformin Combined with Gliclazide in Newly Diagnosed Diabetes Mellitus Type 2 Patients

关键词:  2型糖尿病  MassARRAY  单核苷酸多态性  KCNJ11  rs5219

Key words:  diabetes mellitus type 2  MassARRAY  single nucleotide polymorphism  KCNJ11  rs5219

摘要:

目的 探讨ATM（rs11212617）、KCNJ11（rs5219）、CYP2C9（rs1799853、rs1057910）、TCF7L2（rs12255372、rs290487）及IRS1（rs1801278）位点对二甲双胍及格列齐特联用治疗新诊断2型糖尿病患者疗效的影响。方法 在浙江中医药大学附属嘉兴中医院内分泌科标准化代谢性疾病管理中心门诊就诊，并使用盐酸二甲双胍片和格列齐特缓释片联合治疗的81例新诊断2型糖尿病患者被纳为研究对象，使用MassARRAY技术对上述位点进行分型，并进行为期3个月的随访，对比治疗前后空腹血糖、糖化血红蛋白及空腹胰岛素的变化。结果 上述单核苷酸多态性位点的基因频率符合Hardy-Weinberg遗传平衡，样本代表性良好。rs1799853、rs1057910、rs12255372与rs1801278位点突变频率较低，临床意义欠佳。rs5219 C等位基因纯合患者在治疗后的空腹血糖达标率、空腹胰岛素上升量及糖化血红蛋白下降量上的获益均强于T等位基因携带患者（P<0.05）。而rs11212617和rs290487位点各基因型间并未显示出治疗效果的差异。结论 KCNJ11基因的rs5219位点多态性与盐酸二甲双胍片和格列齐特缓释片联合治疗2型糖尿病的疗效相关，C等位基因纯合患者疗效更为显著，可作为临床治疗2型糖尿病个性化用药的参考。

Abstract:

OBJECTIVE To explore the effect of the polymorphisms of ATM(rs11212617), KCNJ11(rs5219), CYP2C9(rs1799853, rs1057910), TCF7L2(rs12255372, rs290487) and IRS1(rs1801278) on efficacy of metformin and gliclazide combined treatment for diabetes mellitus type 2. METHODS Eighty-one patients with newly diagnosed diabetes mellitus type 2 in Standardized Metabolic Disease Management Center of the Endocrinology Department of of Zhejiang Chinese Medical University Affiliated Jiaxing TCM Hospital were enrolled in this study, and they were treated with metformin hydrochloride tablets and gliclazide modified release tablets. MassARRAY was used to type the above single nucleotide polymorphism(SNP), and followed up for 3 months. Fasting plasma glucose(FPG), glycosylated hemoglobin type Alc(HbA1c) and fasting insulin(FINS) were compared before and after treatment. RESULTS The gene frequencies of all SNPs were compliant to Hardy-Weinberg equilibrium, the samples were well represented. The rs1799853, rs1057910, rs12255372 and rs1801278 had low mutation frequencies with poor clinical significance. The benefits of FPG compliance rate, increase of FINS, decrease of HbAlc after treatment were stronger in patients with homozygous rs5219 C allele than those with T-allele carriers (P<0.05). However, there were no significant differences in treatment effects among the genotypes of rs11212617 and rs290487. CONCLUSION The rs5219 polymorphism of KCNJ11 gene is associated with the efficacy of metformin hydrochloride tablets and gliclazide modified release tablets in treating diabetes mellitus type 2, with a more significant effect observed in individuals homozygous for the C allele. This finding can serve as a reference for personalized medication in clinical treatment of diabetes mellitus type 2.