SUR1 Ser1369Ala多态性与磺脲类药物疗效的相关性

Association between SUR1 Ser1369Ala polymorphism and the efficacy of sulfonylurea

目的观察磺脲类药物受体基因(sulfonylurea receptorSUR1)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。

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 One hundred and four type 2 diabetes patients were selected and orally administered with Gliclazide for 56 days. Venous fasting plasma glucose levels （FPG）, plasma glucose levels half an hour after taking 75 g 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. The glucose-lowering effect of Gliclazide was compared among different groups. If FPG was reduced more than 20%, we define it as effective. People whose blood sugar level was effectively reduced and not significantly reduced were compared to find whether their genotype groups were different. Results The change of FPG, OGH and OGT on day 1 and day 57 among TT, TG and GG genotype groups had no statistically significant difference. 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.