| 引用本文: | 熊烈,姚芳,金利民,宁帆,史汉强,杜书琴,石彦波.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[J].中国现代应用药学,2023,40(24):3431-3438. |
| XIONG Lie,YAO Fang,JIN Limin,NING Fan,SHI Hanqiang,DU Shuqin,SHI Yanbo.Study of KCNJ11 rs5219 Gene Polymorphism on the Efficacy of Metformin Combined with Gliclazide in Newly Diagnosed Diabetes Mellitus Type 2 Patients[J].Chin J Mod Appl Pharm(中国现代应用药学),2023,40(24):3431-3438. |
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| 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 |
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熊烈1,2, 姚芳3,2, 金利民2, 宁帆3,2, 史汉强1,2, 杜书琴4, 石彦波1,2
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1.浙江中医药大学附属嘉兴中医院, 中心实验室, 浙江 嘉兴 314000;2.嘉兴市糖尿病血管病变研究重点实验室, 浙江 嘉兴 314000;3.浙江中医药大学附属嘉兴中医院, 内分泌科, 浙江 嘉兴 314000;4.浙江工业大学药学院, 杭州 310000
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| 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。 |
| 关键词: 2型糖尿病 MassARRAY 单核苷酸多态性 KCNJ11 rs5219 |
| DOI：10.13748/j.cnki.issn1007-7693.20230241 |
| 分类号:R969.4 |
| 基金项目:浙江省医药卫生科技计划项目（2020PY029，2023KY1227）；浙江省基础公益研究计划项目（LGF18H200004）；嘉兴市科技计划项目（2020AY30003）；浙江中医药大学校级科研项目（2022FSYYZZ22） |
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| Study of KCNJ11 rs5219 Gene Polymorphism on the Efficacy of Metformin Combined with Gliclazide in Newly Diagnosed Diabetes Mellitus Type 2 Patients |
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XIONG Lie1,2, YAO Fang3,2, JIN Limin2, NING Fan3,2, SHI Hanqiang1,2, DU Shuqin4, SHI Yanbo1,2
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1.Zhejiang Chinese Medical University Affiliated Jiaxing Traditional Chinese Medicine Hospital, Central Laboratory, Jiaxing 314000, China;2.Jiaxing Key Laboratory of Diabetic Angiopathy Research, Jiaxing 314000, China;3.Zhejiang Chinese Medical University Affiliated Jiaxing Traditional Chinese Medicine Hospital, Department of Endocrine, Jiaxing 314000, China;4.College of Pharmacy, Zhejiang University of Technology, Hangzhou 310000, China
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| 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. |
| Key words: diabetes mellitus type 2 MassARRAY single nucleotide polymorphism KCNJ11 rs5219 |
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