Association Of GLP-1R Gene Polymorphism With Metabolic Markers And GLP-1 Receptor Agonist Efficacy In Type 2 Diabetic Patients

ObjectiveGLP-1 receptor agonists play a therapeutic role in combination with the GLP-1receptor（GLP-1R）.According to existing clinical trials,the GLP-1R gene polymorphism is associated with the efficacy of GLP-1 receptor agonists.Due to the GLP-1R gene polymorphism,there are certain individual differences in patients with different genotypes when given the same dose of medication.The aim of this study was to investigate the association between the GLP-1R rs3765467 and rs10305420 gene polymorphisms and the efficacy of the GLP-1 receptor agonists exenatide and liraglutide in Chinese Han type 2diabetic patients.MethodThis study selected 86 Chinese Han patients with type 2 diabetes who were treated in Qianfoshan Hospital of Shandong Province from July 2015 to September 2018.All cases met the World Health Organization’s T2DM diagnostic criteria.The gene distribution of two SNPs（rs3765467 and rs10305420）in the GLP-1R gene in Chinese Han type 2 diabetic population was examined.According to the inclusion criteria,28 Chinese Han patients with type 2 diabetes were treated with exenatide at a starting dose of 5 ug each time twice daily.After 1 month of treatment,the dose could be increased to 10 ug per day.58 Chinese Han patients with type 2 diabetes were treated with liraglutide at a starting dose of 0.6 mg per day.After at least one week,the dose was increased to 1.2 mg.The basic information of the patient,including the name,hospital number,gender,Age,weight（kg）,height（m）,body mass index BMI（kg/m²）,waist circumference（cm）,glycosylated hemoglobin（Hb A1c）,fasting blood glucose（FPG）,triglyceride（TG）,total cholesterol（TC）Low-density lipoprotein cholesterol（LDL-C）,high-density lipoprotein cholesterol（HDL-C）,systolic blood pressure（SBP）,and diastolic blood pressure（DBP）.Follow-up on time,record changes in physiological and biochemical indicators after treatment.Data were analyzed by SPSS 22.0 software to analyze the association between GLP-1R rs3765467and rs10305420 polymorphisms and the efficacy of GLP-1 receptor agonists exenatide and liraglutide.ResultAmong the 86 Chinese Han patients with type 2 diabetes,the polymorphisms of GLP-1R rs3765467(χ²=2.7×10^-4,P=0.99)and GLP-1R rs10305420（χ²=1.02,P=0.31）were distributed.Meet the Hardy-Weinberg balance.There was no significant difference in the distribution of SNP rs3765467 and rs10305420 genotypes between different genders.Regarding the association between SNP rs3765467 and rs10305420 gene polymorphisms and patients’body mass index,blood glucose,and blood lipid index,there was no significant statistical difference between GG genotype carriers and A allele carriers in rs3765467.Learning differences,but there is a certain trend（P=0.09）.The TG level of the A allele carrier was higher than that of the GG genotype carrier,with a statistically significant difference（P=0.04）;the TC level of the A allele carrier was higher than that of the GG genotype carrier.High with significant statistical difference（P=0.04）.In rs10305420,there was no significant difference in BMI between C genotype carriers and A allele carriers,but there was a certain trend（P=0.09）;CC genotype carriers and A alleles were carried.There was no significant statistical difference in the FPG levels,but there was a certain trend（P=0.09）.Among the 86 Chinese Han patients with type 2 diabetes,the polymorphisms of GLP-1R rs3765467(χ²=2.7×10^-4,P=0.99)and GLP-1R rs10305420（χ²=1.02,P=0.31）meet the Hardy-Weinberg balance.There was no significant difference in the distribution of SNP rs3765467 and rs10305420 genotypes between different genders.Regarding the association between SNP rs3765467 and rs10305420 gene polymorphisms and patients’body mass index,blood glucose,and blood lipid index,there was no significant statistical difference between GG genotype carriers and A allele carriers in rs3765467,but there is a certain trend（P=0.09）;TG levels of A allele carriers are significant higher than those of GG genotype carriers（P=0.04）;A allele Carriers’TC levels were significant higher compared to GG genotype carriers（P=0.04）.For rs10305420,there was no significant difference in BMI between C genotype carriers and A allele carriers,but there was a certain trend（P=0.09）;CC genotype carriers and A alleles were carried.There was no significant statistical difference in the FPG levels,but there was a certain trend（P=0.09）.ConclusionThis study conducted a clinical trial of the association between the GLP-1R gene polymorphism and the efficacy of 86 Chinese Han patients with type 2 diabetes mellitus receiving GLP-1 receptor agonists.The 86 patients with type 2 diabetes in China were highly polymorphic.The GLP-1R rs3765467 gene polymorphism was significantly associated with TG and TC levels in patients.The GLP-1R rs3765467 gene polymorphism was significantly associated with body weight and BMI after GLP-1 receptor agonist treatment.Therefore,GLP-1R rs3765467 gene polymorphism can be used as an important indicator to predict blood lipid levels and body weight changes,and it is of great significance for the treatment of type 2 diabetes and the clinical application of GLP-1 receptor agonists.