目的 探讨液泡蛋白分选受体1(SORCS1)基因rs1416406的多态性对艾塞那肽改善血糖和胰岛功能的影响.方法 研究使用13省市25家大学附属医院参与的CONFIDENCE研究队列数据进行分析.对2010年8月至2012年8月期间101例使用艾塞那肽单药治疗48周的初诊断2型糖尿病患者进行SORCS1基因rs1416406位点分型.多重线性回归分析艾塞那肽治疗48周后糖化血红蛋白(HbA1c)、空腹血糖(FPG)、餐后2h血糖(2 h PG)、体质指数(BMI)、胰岛功能[胰岛素原/胰岛素(PI/I)、急性胰岛素应答(AIR)及处置指数(DI)]等的变化与rs1416406基因型的相关性.结果 艾塞那肽治疗48周后患者HbA1c、FPG、2 hPG和PI/I水平明显降低,DI、AIR明显升高(均P ＜0.05).艾塞那肽治疗后PI/I比值的变化在rs1416406的3种基因型GG、GA、AA间差异有统计学意义(P＜0.05),GG基因型较携带等位基因A的患者PI/I降低更显著(均P＜0.05).多重线性回归分析校正年龄、性别、基线BMI、基线HbA1c和基线PI/I后,rs1416406仍与PI/I变化值显著相关(P＜0.05).DI以及AIR在基线、艾塞那肽治疗48周后和48周变化值在GG、GA、AA间差异均无统计学意义(均P＞0.05).结论 SORCS1基因rs1416406位点单核苷酸多态性影响艾塞那肽的改善β细胞功能的作用,GG基因型患者较携带等位基因A的患者经艾塞那肽治疗后PI/I改善作用更好,提示GG基因型的患者早期选用艾塞那肽治疗获益更多.%Objective To study the relationship between SORCS1 gene rs1416406 and efficiency of exenatide.Methods Between August 2010 and August 2012,a hundred and one newly diagnosed patients with type 2 diabetes mellitus (T2DM) were from CONFIDENCE study covering 25 university-affiliated hospitals in 13 provinces of China.All patients received excnatide treatment for 48 weeks.Hemoglobin A1c (HbA1c),fasting plasma glucose (FPG),body mass index (BMI),oral glucose tolerance test (OGTT)glucose and insulin levels were measured before and after therapy.β-cell function was assessed by fasting proinsulin/insulin (PI/I),disposition index (DI) and acute insulin response (AIR).SORCS1 gene rs1416406 was genotyped by improved multiple ligase detection reaction.The relationship between rs1416406 and the glucose-lowering effect as well as β3-cell function improvement of exenatide was analyzed by multiple linear regression.Results There were statistically significant differences of HbA1c,FPG,2 h plasma glucose (2 h PG),β-cell function (PI/I,DI and AIR) and changes of PI/I in three genotypes (GG,GA,AA) of rs1416406 between baseline and 48-week therapy of exenatide (all P ＜ 0.05).No statistically significant difference was found in changes of HbA1c,FPG,2 h PG,DI,AIR except for PI/I,after stratifying by genotypes of rs1416406.Multiple linear regression analysis showed rs1416406 was significantly associated with the PI/I change (P ＜ 0.05) after adjustment of age,sex,baseline BMI,HbA1 c and PI/I.Conclusion SORCS1 gene rs1416406 was associated with the PI/I improvement induced by exenatide.Patients carrying GG genotype had greater reduction in PI/I after exenatide treatment as compared with those carrying allele A.The results suggests that the newly diagnosed T2DM patients with GG genotype might obtain more benefit from the early treatment of exenatide.
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