埃及患者肠促胰岛素受体基因多态性与 2 型糖尿病的相关性。

Association of incretin receptors genetic polymorphisms with type 2 diabetes mellitus in Egyptian patients.

机构信息

Medical Biochemistry Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.

Internal Medicine Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.

出版信息

J Gene Med. 2017 Sep;19(9-10). doi: 10.1002/jgm.2973. Epub 2017 Sep 21.

DOI:10.1002/jgm.2973

PMID:28744963

Abstract

BACKGROUND

Incretins have opened a new era in type 2 diabetes mellitus (T2DM) pathogenesis. The present study aimed to assess whether there is an association between GIPR rs2302382, GIPR rs1800437 and GLP-1R rs367543060 polymorphisms with T2DM or not and also to determine the effect of these polymorphisms on gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) levels.

METHODS

One hundred and fifty T2DM patients and 150 healthy controls were included in the study. Polymorphisms of GIPR rs1800437, GIPR rs2302382 and GLP-1R rs367543060 were genotyped using restriction fragment length polymorphism (RFLP)-polymerase chain reaction (PCR), multiplex allele-specific PCR and RFLP-PCR respectively. GIP and GLP levels were measured by an enzyme-linked immunosorbent assay.

RESULTS

We found a significant association of both the homozygous AA and the minor allele A of GIPR rs2302382 with T2DM. The frequency of haplotype C(rs2302382) G(rs1800437) was significantly higher in controls than in diabetics; odds ratio (95% confidence interval): 1.99 (1.44-2.75) (p < 0.001), whereas the haplotype A(rs2302382) C(rs1800437) was significantly higher in patients than controls. We did not find any association of GLP-1R rs367543060 polymorphism with T2DM. We found a significant increase in serum total GIP and a significant decrease of GLP-1 levels in T2DM patients.

CONCLUSIONS

We reveal for the first time an association between the GIPR rs2302382 polymorphism and T2DM in Egyptians. Yet, there was no significant association of GIPR rs1800437 or GLP-1R rs367543060 with T2DM risk. The haplotype A (rs2302382) C (rs1800437) was associated with an increased risk of T2DM. Furthermore, there was a significant increase of GIP and a significant decrease of GLP-1 levels when diabetic patients were compared with controls. An important finding was that there was a relationship between both GIPR rs2302382 and rs1800437 variants and their cognate ligand levels.

摘要

背景

肠降血糖素在 2 型糖尿病（T2DM）发病机制中开辟了一个新的时代。本研究旨在评估 GIPR rs2302382、GIPR rs1800437 和 GLP-1R rs367543060 多态性与 T2DM 是否存在关联，以及这些多态性是否对胃抑制多肽（GIP）和胰高血糖素样肽-1（GLP-1）水平有影响。

方法

本研究纳入了 150 例 T2DM 患者和 150 名健康对照者。使用限制性片段长度多态性（RFLP）-聚合酶链反应（PCR）、多重等位基因特异性 PCR 和 RFLP-PCR 分别对 GIPR rs1800437、GIPR rs2302382 和 GLP-1R rs367543060 多态性进行基因分型。采用酶联免疫吸附试验测定 GIP 和 GLP 水平。

结果

我们发现 GIPR rs2302382 纯合 AA 和次要等位基因 A 与 T2DM 显著相关。与对照组相比，糖尿病患者中 GIPR rs2302382 单倍型 C（rs2302382）G（rs1800437）的频率明显更高；比值比（95%置信区间）：1.99（1.44-2.75）（p<0.001），而 GIPR rs2302382 单倍型 A（rs2302382）C（rs1800437）在患者中明显高于对照组。我们没有发现 GLP-1R rs367543060 多态性与 T2DM 之间存在任何关联。我们发现 T2DM 患者血清总 GIP 水平显著升高，GLP-1 水平显著降低。

结论

我们首次揭示了 GIPR rs2302382 多态性与埃及人 T2DM 之间的关联。然而，GIPR rs1800437 或 GLP-1R rs367543060 与 T2DM 风险之间没有显著关联。单倍型 A（rs2302382）C（rs1800437）与 T2DM 风险增加相关。此外，与对照组相比，糖尿病患者的 GIP 水平显著升高，GLP-1 水平显著降低。一个重要的发现是，GIPR rs2302382 和 rs1800437 变体及其同源配体水平之间存在关系。