SUR1和KCNJ11基因多态性与磺脲类药物继发性失效的相关性研究  

Relations of SUR1 and KCNJ11 gene polymorphisms with secondary failure of sulfonylurea in type 2 diabetes

作　　者：邵倩[1,2] 班博[2] 施锦绣 

机构地区：[1]山东大学医学院,山东济南250012 [2]济宁医学院附属医院内分泌科,山东济宁272029 [3]上海人类基因组研究中心,上海201203

出　　处：《中国药理学通报》2013年第7期927-931,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学青年基金资助项目(No 30900828)

摘　　要：目的探讨磺脲类药物受体1(SUR1)基因的外显子16-3c/t、内向整流性钾通道(potassium inwardly-rectifying channel subfamily J,member 11,KCNJ11)基因的E23K变异与2型糖尿病(type 2 diabetes mellitus,T2DM)患者磺脲类药物继发性失效(secondary failure of sulfonylurea,SFS)的关系。方法选取山东地区T2DM患者200例,其中磺脲类药物有效者114例,SFS者86例,运用SNaPshot技术(ABI Biosystem,USA)对SUR1 16-3c/t、KCNJ11 E23K进行基因分型。结果 SUR1 16-3c/t和KCNJ11 E23K等位基因的发生频率均符合Hardy-Weinberg平衡;KCNJ11 E23K各基因型的分布在SFS组及有效组之间差异无统计学意义(P>0.05);SUR116-3c/t各基因型的分布在SFS组和有效组之间差异有统计学意义(P<0.01),且"t"等位基因的频率在SFS组明显增高[比值比(OR)=1.87,95%可信区间(CI)为1.23～2.85,P<0.01]。Logistic回归分析中,校正性别、年龄、BMI、F-C肽、TG、TC、HDL-C、LDL-C后,SUR1 16-3c/t的t/t基因型是SFS发生的独立危险因素[比值比(OR)=2.82,95%可信区间(CI)为1.57～5.07,P<0.01]。结论 SUR1外显子16-3c/t多态性可能与山东地区磺脲类药物继发性失效有明显相关性。Aim To investigate whether the polymorphismsofexon16-3c/tinSURlandE23KinKCNJ11 are correlated with secondary failure of sulfonylurea in type 2 diabetes mellitus. Methods The association of two SNPs in SUR1 and KCNJll was studied by genoty- ping them with ABI SNaPshot Multiplex System in 114 patients with sulfonylurea effective, and 86 patients with secondary failure of sulfonylurea. Results The genotype frequencies distribution of KCNJll E23K were found to show no significant differences between SU failure group and SU effective group （P 〉 0. 05 ）. There were significant differences in the distributive frequency of the SUR1 16-3 c/t polymorphism between SU failure group and SU effective group （P 〈0.01 ） . The risk allele ＂ t＂ frequencies in SU failure group were significantly higher than that in SU effective group （ odds ratio = 1.87,95% confidence interval ： 1.23 2. 85, P 〈0. 01 ）. Adjustment for age, gender, BMI, fasting C-peptide, triglyeeride, cholesterin, high-den- sity lipoprotein cholesterol, low density lipoprotein in cholesterol a logistic regression analysis did not change this association （odds ratio = 2. 82, 95% eonfidenee interval： 1.57 - 5.07, P 〈 0. 01 ）. Conclusion These data demonstrate that the polymorphism of exon 16-3c/t in SUR1 may be assoeiated with secondary failure of sulfonylurea in type 2 diabetes mellitus in Shandong Province.

关 键 词：2型糖尿病 磺脲类药物 基因多态性 SNaPshot技术 SUR1 KCNJ11 

分 类 号：R394.2[医药卫生—医学遗传学] R587.102.6[医药卫生—基础医学]