K_(ATP)通道基因多态性与2型糖尿病及磺脲类药物疗效的相关性

Association between ATP-sensitive K^+ channel gene polymorphism and therapeutic responsiveness of sulfonylurea drug in type 2 diabetes

目的探讨ATP敏感性钾(KATP)通道基因ABCC8、KCNJ11单核苷酸多态性(SNPs)与山东汉族2型糖尿病(T2DM)遗传易感性的关系,并观察与磺脲类药物疗效的相关性。方法选取山东济宁地区的正常对照组(NC组)100例,T2DM组200例,并将T2DM组分为磺脲类继发失效(SFS)组86例,有效组114例,运用ABI SNaPshot技术(ABI Biosystem,USA)对ABCC8、KCNJ11基因上2个典型的SNPs进行基因分型。结果(1)ABCC8基因rs1799854在NC组和T2DM组等位基因频率及基因型构成差异有统计学意义(P﹤0.05),T2DM组危险等位基因t显著高于NC组(P﹤0.05);KCNJ11基因rs5219在NC组和T2DM组等位基因频率及基因型构成差异无统计学意义(P﹥0.05)。(2)在200例服用磺脲类降糖药物的T2DM患者中,仅发现ABCC8基因rs1799854在磺脲类继发失效组及有效组等位基因频率及基因型构成差异有统计学意义(P﹤0.05),且"t"等位基因的频率在失效组人群中显著增高(P<0.05)。结论 ABCC8基因rs1799854 t/t多态性可能显著增加山东汉族人群T2DM遗传易感性,并且可能与SFS相关;KCNJ11基因rs5219可能与山东地区T2DM遗传易感性及磺脲类药物疗效无关。

Objective To explore the relationship between the polymorphism of ABCCS, KCNJll gene that encode ATP-sensitive K ＋ channel and type 2 diabetes mellitus （T2DM）, and the therapeutic responsiveness was observed on 200 people with T2DM. Methods The 100 normal control group and 200 T2DM patients living in Jining of Shandong province were recruited. 200 T2DM patients were divided into secondary failure to sulfonylurea（SFS） and sulfonylureas effective groups. The representative SNPs in ABCC8 and KCNJ11 were studied by ABI SNaPshot Multiplex System. Results There was significant difference in allele frequencies and the construction of genotype frequen- cies of ABCC8 rs1799854 between NC and T2DM groups（ P 〈 0. 05 ）. The risk allele t frequency in T2DM group was significantly higher than that in NC group;there was no significant difference in allele frequencies and the construction of genotype frequencies of KCNJll rs5219 between NC and T＇2DM groups （P 〉 0. 05 ）. In 200 T2DM patients treated with sulfonylurea drug, only ABCC8 rs1799854 had significant difference in allele frequencies and the construction of genotype between SFS and sulfonylurea effective groups （ P 〈 0. 05 ）, the risk allele t frequency in SFS group was significantly higher than that in sulfonylurea effective group （P 〈 0. 05）. Conclusions The rs1799854 t/t polymorphisms of ABCC8 gene might be significantly increase susceptibility of T2DM in Han people of Shandong province, and might be associated with SFS. No relationship between KCNJ11 rs.5219 polymorphism and T2DM has been found in Han people of Shandong province, and might not be associated with SFS.