SLC22A1、SLC22A4基因多态性与2型糖尿病患者二甲双胍疗效的相关性

Association between SLC22A1,SLC22A4 gene polymorphisms and therapeutic efficacy of metformin in type 2 diabetes mellitus

目的探讨甘肃地区2型糖尿病(T2DM)患者SLC22A1 rs628031与SLC22A4 rs272893位点基因多态性与二甲双胍疗效的相关性。方法以300例T2DM患者与300例健康对照者为研究对象,用PCR-限制性片段长度多态性(PCR-RFLP)的方法检测2个基因多态性位点突变在甘肃汉族人群中的分布频率。选取其中新诊断的T2DM患者105例,接受每日口服500 mg二甲双胍的治疗,随访90 d;根据基因型分组,分析空腹血糖(FPG)、餐后2 h血糖(2h PPG)及糖化血红蛋白(Hb A1c)变化情况与各基因型的关系。结果 SLC22A1 rs628031与SLC22A4 rs272893在T2DM患者和健康对照者之间的分布频率差异均无统计学意义(P均>0.05)。SLC22A1 rs628031 AG型与AA型、GG型与AA型FPG、Hb A1c治疗前后变化幅度差异均有统计学意义(P均<0.05)。SLC22A4 rs272893基因多态性中GG型与AA型FPG治疗前后变化幅度差异有统计学意义(P<0.05)。结论 SLC22A1rs628031和SLC22A4 rs272893基因多态性位点突变与2型糖尿病患者二甲双胍的疗效存在一定的关联。

Objective To evaluate the correlations of SLC22A1 rs628031 and SLC22A4 rs272893 polymorphisms with efficacy of metformin in type 2 diabetes mellitus（ T2DM） patients in Gansu,China. Methods Three hundred T2 DM patients and 300 healthy subjects were selected to detect allele frequencies of 2 polymorphisms（ SNPs） among Chinese Han population in Gansu province. Genotypes of the 2 SNPs in all selected individuals were identified by polymerase chain reaction-restriction fragment length polymorphism（ PCR-RFLP）. Among them 102 newly diagnosed T2 DM patients were took metformin monotherapy（ 500 mg/d） for 90 consecutive days. The subjects were divided into different groups according to genotypes of the two SNPs and analyze the relationships between each genotype and changes of the fasting plasma glucose（ FPG）,2 h postprandial glucose（ 2h PPG） and glycosylated hemoglobin（ Hb A1c）. Results No significant difference of allele frequencies of SLC22A1 rs628031 and SLC22A4 rs272893 between T2 DM patient and healthy subjects were found（ all P 〉 0. 05）. Compared with AA genotype,SLC22A1 rs628031 AG and GG genotyped patients showed significant decrease of FPG（ P 〈 0. 05） and Hb A1c（ P 〈 0. 05）. Compared with AA genotype,SLC22A4 rs272893 GG genotyped patients showed significant decrease of FPG（ P 〈 0. 05）. Conclusion The polymorphisms of SLC22A1 rs628031 and SLC22A4rs272893 may associate with metformin efficacy in T2 DM patients.