GLP1R rs3765467 Polymorphism Is Associated with the Risk of Early Onset Type 2 Diabetes

Yunyun Fang; Jingjing Zhang; Linlin Ji; Chaoyu Zhu; Yuanyuan Xiao; Qingge Gao; Wenjing Song; Li Wei

doi:10.1155/2023/8729242

GLP1R rs3765467 Polymorphism Is Associated with the Risk of Early Onset Type 2 Diabetes

Int J Endocrinol. 2023 Dec 14:2023:8729242. doi: 10.1155/2023/8729242. eCollection 2023.

Authors

Yunyun Fang¹, Jingjing Zhang², Linlin Ji¹, Chaoyu Zhu¹, Yuanyuan Xiao¹, Qingge Gao¹, Wenjing Song¹, Li Wei¹

Affiliations

¹ Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, 600 Yishan Road, Shanghai 200233, China.
² National Demonstration Center for Experimental Fisheries Science Education, Shanghai Ocean University, 999 Hucheng Huan Road, Lingang New City, Shanghai 201306, China.

Abstract

Objective: To investigate the relationship between glucagon-like peptide-1 receptor gene polymorphisms and susceptibility to early onset type 2 diabetes.

Methods: Samples from 316 type 2 diabetes patients with early onset type 2 diabetes (n = 137) and late-onset type 2 diabetes (n = 179) and 145 nondiabetic individuals were analyzed. Multiplex PCR combined with resequencing Hi-Reseq technology was used to detect single nucleotide polymorphisms of the glucagon-like peptide-1 receptor gene, and the allele frequency, genotype distribution, and clinical parameters were analyzed between each diabetes subgroup and the control group.

Results: Sixteen single nucleotide polymorphisms were identified in the exonic region of the glucagon-like peptide-1 receptor gene according to the minor allele frequency (MAF > 0.05) in the participants. Among these, the glucagon-like peptide-1 receptor rs3765467 (G⟶A) mutation was statistically associated with early onset type 2 diabetes. Compared with that of the GG carriers, carriers of genotype AA at rs3765467 had a decreased risk of early onset type 2 diabetes after adjusting for sex and body mass index. In the dominant model, the frequencies of the rs3765467 AA + GA genotype were significantly decreased in the early onset type 2 diabetes group, and carriers of genotype AA + GA at rs3765467 had a decreased risk of early onset type 2 diabetes after adjusting for sex and body mass index. Moreover, fasting C peptide levels were significantly higher in GA + AA genotype carriers than those in GG genotype carriers.

Conclusion: The glucagon-like peptide 1 receptor rs3765467 polymorphism was significantly associated with age at type 2 diabetes diagnosis and thus may be used as a marker to screen and detect individuals at risk of developing early onset type 2 diabetes.