The role of GLP1R gene polymorphism in diabetic nephropathy in patients with type 2 diabetes

IF 1 Q4 GENETICS & HEREDITY

Gene Reports Pub Date : 2025-03-22 DOI:10.1016/j.genrep.2025.102205

Azza A. Gomaa , Amany M. Zeid , Ibrahim M. Nagy

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引用次数: 0

Abstract

Background

Diabetic nephropathy (DN) is a prevalent microangiopathic problem of T2DM and is a key cause of kidney damage, which affects a large portion of patients with type 2 diabetes mellitus (T2DM). Genetic predisposition plays a crucial role in the development of DN.

Aim

We investigated the effect of glucagon-like peptide 1 receptor (GLP1R) genetic polymorphisms on the susceptibility to DN in patients with T2DM.

Methods

A total of 294 T2DM patients with DN were enrolled: non-DN Group I and DN Group II. Two tagging single nucleotide polymorphisms (tSNPs) of the GLP1R gene were selected. SNPs were genotyped via polymerase chain reaction, and the results were correlated with DN.

Results

Patients with T2DM with The GA and AA genotypes of rs3765467 were linked to higher DN risk, with odds ratios (ORs) of 1.975 (p = 0.017) and 4.175 (p = 0.034), respectively, while the CT genotype of rs10305420 showed an OR of 1.719 (p = 0.031). Both SNPs were correlated with altered lipid profiles, renal function markers, and elevated albumin/creatinine ratio (UACR) (p < 0.05). The A-T haplotype was significantly related to a greater risk of DN in T2DM patients.

Conclusions

These results recommend that GLP1R genetic polymorphisms play a crucial role in the pathogenesis of DN, and the identified variants may serve as valuable genetic biomarkers for predicting DN risk in T2DM patients.

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GLP1R基因多态性在2型糖尿病患者糖尿病肾病中的作用

背景：糖尿病肾病（DN）是T2DM患者常见的微血管病变，是造成肾脏损害的主要原因，影响了很大一部分2型糖尿病（T2DM）患者。遗传易感性在DN的发生中起着至关重要的作用。目的探讨胰高血糖素样肽1受体（GLP1R）基因多态性对T2DM患者DN易感性的影响。方法共纳入294例T2DM合并DN患者：非DN组I和DN组II。选择GLP1R基因的两个标记单核苷酸多态性（tssnp）。通过聚合酶链反应对snp进行基因分型，结果与DN相关。结果rs3765467基因型为GA和AA型的T2DM患者DN风险较高，比值比分别为1.975 （p = 0.017）和4.175 (p = 0.034)，而rs10305420基因型的比值比为1.719 （p = 0.031）。这两个snp都与脂质谱改变、肾功能指标和白蛋白/肌酐比值（UACR）升高相关(p <；0.05)。a - t单倍型与T2DM患者发生DN的风险显著相关。结论GLP1R基因多态性在DN的发病机制中起着至关重要的作用，所鉴定的变异可能作为预测2型糖尿病患者DN风险的有价值的遗传生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Gene Reports Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.30

自引率

7.70%

发文量

246

审稿时长

49 days

期刊介绍： Gene Reports publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses. Gene Reports strives to be a very diverse journal and topics in all fields will be considered for publication. Although not limited to the following, some general topics include: DNA Organization, Replication & Evolution -Focus on genomic DNA (chromosomal organization, comparative genomics, DNA replication, DNA repair, mobile DNA, mitochondrial DNA, chloroplast DNA). Expression & Function - Focus on functional RNAs (microRNAs, tRNAs, rRNAs, mRNA splicing, alternative polyadenylation) Regulation - Focus on processes that mediate gene-read out (epigenetics, chromatin, histone code, transcription, translation, protein degradation). Cell Signaling - Focus on mechanisms that control information flow into the nucleus to control gene expression (kinase and phosphatase pathways controlled by extra-cellular ligands, Wnt, Notch, TGFbeta/BMPs, FGFs, IGFs etc.) Profiling of gene expression and genetic variation - Focus on high throughput approaches (e.g., DeepSeq, ChIP-Seq, Affymetrix microarrays, proteomics) that define gene regulatory circuitry, molecular pathways and protein/protein networks. Genetics - Focus on development in model organisms (e.g., mouse, frog, fruit fly, worm), human genetic variation, population genetics, as well as agricultural and veterinary genetics. Molecular Pathology & Regenerative Medicine - Focus on the deregulation of molecular processes in human diseases and mechanisms supporting regeneration of tissues through pluripotent or multipotent stem cells.