磺脲类受体1基因多态性对磺脲类降糖药物作用的影响

Influence of gene polymorphism of sulphonylurea receptor 1 on glucose-reducing effect of gliclazide

目的:研究磺脲类受体1(sulphonylurea receptor1,SUR1)基因上的常见单核苷酸多态性(single nucleotide poly-morphism,SNP)16-3c/t和S1369A对格列齐特降糖作用的影响。方法:就诊于本院门诊的北方汉族2型糖尿病患者115名,服用格列齐特治疗8周(初始剂量40mg bid,根据第15天和第29天空腹血糖值调整剂量,每次增加40mg,最大剂量为120mg bid)。治疗前后分别检测空腹血浆血糖(fasting plasma glucose,FPG)、糖化血红蛋白(HbA1c)、基础胰岛素、肝肾功等指标,计算HOMA-B和HOMA-IR指数,治疗期间定期进行随诊。用荧光水解探针技术检测患者SUR1基因16-3c/t及S1369A多态性,比较不同基因型患者格列齐特疗效的差异。结果:(1)共有101例患者完成全部试验,其中16-3c/t多态性中c等位基因频率为0.56,t等位基因频率为0.44;S1369A多态性中S等位基因频率0.58,A等位基因频率为0.42;(2)各基因型患者经过治疗FPG、HbA1c、HOMA-B指数均明显改善(P<0.05),HOMA-IR指数没有明显变化(P>0.05);(3)16-3t/t患者HbA1c及HOMA-B指数的改善程度明显高于16-c/c及16-3c/t患者(P<0.05),S1369A多态性的各基因型患者比较上述指标改善程度没有显著性差异(P>0.05)。结论:SUR1基因多态性会对格列齐特的降糖疗效起修饰作用,这种作用可能与SNP的位置有关。

Objective： To study the common single nucleotide polymorphism （SNPs） of sulphonylurea receptor 1 （SUR1） gene （16-3c/t and S1369A） and its relationship with the glucose-reducing effect of gliclazide. Methods; A total of 115 patients with type 2 diabetes were enrolled in this 8-week, open-label, cohort study. All patients were required to take gliclazide for 8 weeks. FPG, HbAlc and insulin were assayed before and after therapy and HOMA-B and HOMA IR indices were calculated to assess the therapeutic effects of gliclazide. The gene polymorphism of SUR1 was analyzed by Taq-Man technology and the effects of gliclazide were compared between patients with different phenotypes. Restults： （1） The study was completed in 101 of the 115 patients and the frequencies of c and t alleles were 0.54 and 0.44, A and S were 0.58 and 0.42, respectively. （2） FPG, HbAlc and HOMA B indices were significantly improved after therapy in patients with all kinds of genotypes （P^0. 05）; HOMA-IR indices had no significant change after therapy（P〉0.05）. （3） The changes of HbAlc and HOMAB indices of t/t group were more obvious than those of c/c and c/t groups （P〈0.05）. S1369A polymorphism had no association with the effect of gliclazide（P〉0.05）. Conclusion： The polymorphism of SUR1 can influence the glucose-reducing effect of gliclazide and this influence might be associated with loci of SNPs.