关键词: 2型糖尿病, 胰高血糖素样肽1受体, 利拉鲁肽, 遗传变异, 疗效

Abstract:

Objective To investigate the effect of genetic variations in glucagon ⁃like peptide ⁃ 1 receptor （GLP1R）on the efficacy of liraglutide monotherapy for patients with type 2 diabetes. Methods A total of 219 patients with type 2 diabetes who received liraglutide monotherapy were included retrospectively. Changes in HbA1c，fasting plasma glucose（FPG），weight，body mass index（BMI）and waist ⁃to ⁃hip ratio（WHR）before and after treatment was collected and analyzed. Additionally，the association between efficacy and genotype status of genetic variation in GLP1R was analyzed subsequently. And the mRNA expression of GLP1R according to geno⁃ type status of polymorphism was analyzed. Results Patients showed significant improvement in all indicators of diabetes and weight before and after liraglutide treatment. The results of association analysis between efficacy indi⁃ cators and A131P polymorphism in GLP1R showed that the changes of HbA1c，FPG，weight，BMI and WHR were more significant among patients with GG genotype，and all the differences were statistically significant（P < 0.01）. Furthermore，the HbA1c achievement rate of patients with GG and GA/AA genotype was 64.6% and 44.4% ， respectively（χ2 = 7.488，P = 0.006）. Additionally，the expression of GLP1R mRNA in patients with GA/AA geno⁃ type was relatively lower than that in patients with GG genotype，and it was statistically significant（t = 4.081，P < 0.001）. Conclusion Polymorphism of A131P in GLP1R might compromise the efficacy of liraglutide through the mediation of mRNA expression. And the conclusion should be confirmed in prospective clinical trials subsequently.

Key words:

type 2 diabetes, glucagon like peptide 1 receptor, liraglutide, genetic variation, efficacy