胰高血糖素样肽1受体基因遗传变异对利拉鲁肽治疗2型糖尿病患者疗效的影响  

Effect of genetic variations in glucagon-like peptide-1 receptor on liraglutide monotherapy for patients with type 2 diabetes

作　　者：任丽君 高红红 宋瑞捧 REN Lijun;GAO Honghong;SONG Ruipeng(Department of Endocrinology,the No.3 Pro-vincial People′s Hospital of He′nan Province,Zhengzhou 450002,China)

机构地区：[1]河南省直第三人民医院内分泌科,郑州450002

出　　处：《实用医学杂志》2023年第2期164-169,共6页The Journal of Practical Medicine

基　　金：河南省医学科技攻关计划(联合共建)项目(编号:LHGJ20190860)。

摘　　要：目的 探讨胰高血糖素样肽1受体基因(GLP1R)遗传变异对利拉鲁肽治疗2型糖尿病患者的临床疗效的影响。方法 回顾性纳入接受利拉鲁肽单药治疗的219例2型糖尿病患者,记录患者治疗前后的糖化血红蛋白(HbA1c)、空腹血糖(FPG)、体质量、体质指数(BMI)和腰臀比(WHR)的指标变化。此外,比较GLP1R基因多态性位点和疗效指标的关联性,分析GLP-1R基因遗传变异和mRNA表达的相关性。结果 接受利拉鲁肽治疗后患者的各项指标均有了显著的改善。GLP1R基因A131P位点和临床指标的关联分析结果提示:GG基因型患者的HbA1c、FPG、体质量、BMI和腰臀比几项指标下降变化更明显,且对比差异均有统计学意义(P <0.01)。GG和GA/AA基因型患者的HbA1c达标率分别为64.6%和44.4%(χ^(2)=7.488,P=0.006)。此外,GA/AA基因型患者的GLP1R基因mRNA的表达比GG型患者的相对较低,差异有统计学意义(t=4.081,P <0.001)。结论 GLP1R基因A131P位点可能通过介导了基因mRNA表达从而影响了利拉鲁肽治疗的临床疗效。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 219patients 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 m RNA expression of GLP1R according to genotype 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 indicators 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(χ^(2)= 7.488,P = 0.006). Additionally,the expression of GLP1R mRNA in patients with GA/AA genotype 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.

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 

分 类 号：R587.1[医药卫生—内分泌]