基础医学与临床 ›› 2007, Vol. 27 ›› Issue (5): 521-524.

• 研究论文 • 上一篇    下一篇

SUR1Ser1369Ala多态性与磺脲类药物疗效的相关性

杨毅(北京) 郭丽敏 杨金奎   

  1. 首都医科大学附属北京同仁医院内分泌科 首都医科大学附属北京同仁医院 首都医科大学附属北京同仁医院
  • 收稿日期:2006-12-14 修回日期:2007-03-05 出版日期:2007-05-25 发布日期:2007-05-25
  • 通讯作者: 杨毅(北京)

Association between the SUR1 Ser1369Ala polymorphism and the efficacy of sulfonylurea

  

  • Received:2006-12-14 Revised:2007-03-05 Online:2007-05-25 Published:2007-05-25

摘要: 目的 观察磺脲类药物受体基因(sulfonylurea receptor SUR1)第33号外显子上的一处错义突变(Ser1369Ala,TCC→GCC)与格列齐特降糖效果之间的关系。方法 选取2型糖尿病患者104人,口服格列齐特56天,监测空腹血浆葡萄糖、服糖后30min及2h血糖水平,检测Ser1369Ala多态性位点基因型,根据基因型不同建立相加模型、显性模型及隐性模型。分析降糖有效及无效者的基因型有无差异。结果 TT,TG和GG型组第1天与第57天空腹血浆葡萄糖、服糖后30min及2h血糖无明显下降;将TG型和GG型合并为一组与TT组比较第57天静脉空腹血糖显著下降(P<0.05);将TT型和TG型合并为一组与GG型比较无差别。结论 携有SUR1基因的Ser1369Ala多态性位点G等位基因的人群对磺脲类药物比较敏感。

Abstract: Objective To investigate the association between a missense mutation (T/G, Ser 1369 Ala) in exon 33 of sulfonylurea receptor 1(SUR1) gene in type 2 diabetes patients and the glucose-lowering effect of Gliclazide. Methods 104 type 2 diabetes patients were selected and administered with Gliclazide orally for 56 days. Venous fasting plasma glucose levels (FPG), plasma glucose levels half an hour after taking 75g glucose (OGH) and two hours (OGT) after taking Gliclazide were measured. Ser1369Ala polymorphism genotypes(TT, TG, GG) of SUR1 gene were determined by Taqman method. 104 patients were grouped based on their different genotypes. The glucose-lowering effect of Gliclazide was compared among different groups. If FPG ★通讯作者:yangjk@trhos.com was reduced more than 20%, we took it as effective. People whose blood sugar level was effectively reduced and not effectively reduced were compared to see whether their genotype groups were different. Results The percent change of FPG,OGH and OGT on day one and day 57 among TT,TG and GG genotype groups had no statistically significant difference. Patients carrying one or two copies of the G allele displayed significantly larger percent decrease values of FPG (P<0.05) compared with patients carrying the TT genotype. There was no statistically significant difference of the efficacy of Gliclazide in recessive model (TT+TG vs.GG). The combination of TG and GG was more effective in reducing blood sugar level than TT. Conclusion Patients carrying one or two copies of the G allele were more sensitive to Gliclazide than patients carrying T allele.