[Association between SORCS1 rs1416406 and therapeutic effect of exenatide]

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 exenatide 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 β-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, HbA1c 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 .