Research On Relationship Between GLP-1 Receptor Gene Exon Polymorphisms And Type 2 Diabetes Mellitus In Shanghai Han Population

Aim: Glucagon like peptide-1 receptor gene plays an important role in the regulation of glucose homeostasis.Recent studies have found that GLP-1R gene polymorphism is associated with insulin secretion and susceptibility to diabetes mellitus.At present,the research of GLP-1R gene polymorphism distribution in Chinese population is very limited.This paper will explore the relationship between GLP-1R gene polymorphism and insulin-like peptide-1 receptor in Chinese population through SNP genotyping and data analysis.Objective to investigate the relationship between GLP-1R gene polymorphism and susceptibility to type 2 diabetes mellitus(T2DM),and to provide a theoretical basis for predicting the risk of T2 DM,identifying high-risk groups and the exploring etiology of T2 DM.Methods: A total of 318 Han patients with T2 DM and 145 non-diabetic controls in Shanghai were enrolled.The polymorphisms of GLP-1R gene was detected with Multiplex PCR-High throughput sequencing.Differences in frequencies of genotypes and alleles,as well as other clinical feature between two groups were analyzed by Chi square test,independent sample t test,nonparametric test and unconditional logistic regression analysisResults :(1)23 SNPs were identified,of which GLP-1R-rs3765467(G/A)polymorphism was significantly associated with T2DM(P = 0.005).(2)Compared with the control group,body mass index,fasting blood glucose,2hours plasma glucose,fasting insulin,glycated hemoglobin,glycated albumin,low density lipoprotein cholesterol,triglyceride and HOMA-Insulin resistance index were significantly increased in T2 DM group(P < 0.001).High density lipoprotein cholesterol and HOMA-β were lower than those in the control group(P < 0.001).(3)The genotype frequencies of GG,GA and AA at rs3765467 in T2 DM group and control group were 63%,30%,7% and 48%,42% and 10%,respectively.The allele frequencies of G and A in T2 DM group and control group were 78%,22% and 69%,31%.The frequency of G allele was significantly higher in T2 DM group(P = 0.005).Compared with A allele carriers,the risk of G allele carriers was significantly higher(OR = 1.569,95% CI: 1.148～2.144,P = 0.005).In the dominant model,the risk of T2 DM was 1.841-fold higher in individuals with rs3765467 GG genotype than in individuals with GA / AA genotype(OR = 1.841,95% CI: 1.237-2.739,P = 0.003).Multivariate logistic regression analysis was performed with T2 DM as the dependent variable,rs3765467 allele,age,gender,body mass index,systolic blood pressure,triglyceride and high density lipoprotein cholesterol as the independent variables.The results showed that G allele was an independent risk factor for T2DM(OR = 1.705,P = 0.008).In the clinical feature analysis,the glycosylated albumin level of GG carriers was significantly higher than that of GA/AA carriers(21.69% vs.19.34%,P < 0.05),while other clinical indicators had no significant difference between the two genotypes(P > 0.05).(4)In male population,the frequencies of GG,GA and AA at rs3765467 locus in T2 DM group and control group were 67%,28%,6% and 47%,43% and 10%,respectively.The frequencies of G and A alleles in T2 DM group and control group were80%,20% and 66%,34% respectively.The frequency of G allele in T2 DM group was higher than that in control group,and the risk of G allele carriers was higher than that of a allele carriers(OR = 2.075,95% CI: 1.291～3.336,P = 0.003).In the dominant model,the risk of GA + AA genotype was 2.615 times higher than that of GG genotype(95%CI: 1.413～4.841,P = 0.002).In the analysis of clinical feature,compared with GA + AA genotype carriers,the fasting blood glucose level of GG genotype carriers was significantly higher(8.25 ± 2.55 vs.7.34 ± 2.46 mmol/L,P < 0.05),and the glycosylated hemoglobin level was significantly higher(8.81% vs.7.89%,P < 0.05),while other clinical indicators had no significant difference between the two genotypes.(5)In T2DM group,early onset T2DM(EOD)was defined when the age of diagnosis was less than 45 years old,and late onset T2DM(LOD)was defined when the age of diagnosis was more than 45 years old.The G and A allele frequencies of rs3765467 were 83% and 17% in EOD group,and 69% and 31% in control group,respectively.The G allele frequency of rs3765467 in EOD group was significantly higher than that of A allele(OR = 2.085,95 % CI: 1.399～3.107,P < 0.001),In the dominant model,the risk of T2 DM increased by 2.423 times(95 % CI: 1.488～3.947,P < 0.001)in individuals with rs3765467 GG genotype compared with those with GA + AA genotype.In the analysis of clinical feature,the fasting C-peptide level of GG genotype carriers was significantly higher than that of GA + AA genotype carriers(1.7 vs.2.3 ng/m L,P < 0.05),while there was no significant difference in other clinical indicators between the two groups(P >0.05).Conclusion: GLP-1R rs3765467 polymorphism is associated with T2 DM susceptibility in Shanghai population.G allele increases the risk of T2 DM,especially in male and EOD population.The G allele of rs3765467 may be associated with impaired secretion of βcells and affect the blood glucose level of the population.