【摘要】 目的:观察天津汉族2型糖尿病患者服用格列齐特后的药物疗效及其与磺脲类受体(SUR)1基因33外显示Ser1369Ala多态性分布的关联性。方法:选择确诊时间<5年,最近2个月降糖药物治疗时间累计<l周,且最近1周无任何降糖药治疗史的患者166例。空腹血糖7.8～15.0 mmol/L,体质量指数<28 kg//m2。给予格列齐特治疗8周,观察药物疗效。取静脉血提取DNA,Taqman荧光定量PCR法测定SUR1基因33外显子Ser1369Ala的多态性。据单核苷酸碱基多态性分为tt、cc、ct组进行药效的比较。结果:tt组患者空腹胰岛素和HOMA模型β细胞功能指数低于cc、ct组,具有tt基因型和t等位基因的患者药物失效率明显高于具有cc、ct基因型及c等位基因的患者。结论:SUR1基因33外显子Ser1369Ala的多态性与磺脲类药物的原发性失效相关,可能是由于tt基因型影响了SUR1的功能,导致胰岛素分泌减少所致。更多还原

【Abstract】 Objective: To investigate the therapeutic effects of gliclazide on type 2 diabetic patients in Han population in Tianjin,and to study the correlativity between the therapeutic effects and Ser1369Ala gene polymorphism of sulfonylurea receptor1.Methods: A hundred and sixty-six patients,diagnosed type 2 diabetes mellitus less than 5 years,not took any hypoglycemic medicines less than a week in recent 2 months and not took any hypoglycemic medicines in the latest week,were involved in the study.Their fasting plasma glucose levels were between 7.8～15.0mmol/L and body mass indexes were less than 28 kg/m2.All patients received gliclazide treatment for 8 weeks.Genomic DNA was extracted from venous blood samples.The sulfonylurea receptor 1 gene polymorphism was determined by Taqman fluorescent quantitation polymerase chain reaction analysis.According to single nucleotide polymorphism they were divided into tt,cc and ct groups.Results: Fasting insulin and homeostasis model assessment of β cell function index in tt group were lower than those in ct and cc groups.Inefficient ratio of patient possessing tt genotype and t allel was markedly higher than those in cc and ct groups.Conclusion: Ser1369Ala gene polymorphism of sulfonylurea receptor 1 is related to primary failure of gliclazide,which possibly owing to tt genotype influencing the function of sulfonylurea receptor 1 and reducing the secretion of β cell.更多还原