NRF2 基因外显子单核苷酸多态性 rs182428269 与糖尿病足溃疡的相关性分析。

Analysis of the Exonic Single Nucleotide Polymorphism rs182428269 of the NRF2 Gene in Patients with Diabetic Foot Ulcer.

机构信息

Department of Biotechnology and SRM Research Institute, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, India.

Department of Zoology, College of Science King Saud University, Riyadh, Saudi Arabia.

出版信息

Arch Med Res. 2021 Feb;52(2):224-232. doi: 10.1016/j.arcmed.2020.10.011. Epub 2020 Nov 5.

DOI:10.1016/j.arcmed.2020.10.011

PMID:33160752

Abstract

BACKGROUND

The pivotal role of Nuclear factor erythroid-2-related factor 2 (NRF2) in redox homeostasis and wound healing has been well documented. However, the genetic mechanisms that regulate NRF2 in type 2 diabetes and diabetic foot ulcers remain unexplored. The present study investigated the association of single nucleotide polymorphism rs182428269 (-127 C/T) in subjects with type 2 diabetes and diabetic foot ulcers.

METHODS

This cross-sectional study comprised 400 participants that included group I: normal glucose tolerant subjects (NGT, n = 150), group II: type 2 diabetes mellitus subjects (T2DM, n = 150) and group III: infected diabetic foot ulcer subjects (DFU, n = 100). The non-synonymous SNP rs182428269 was selected based on in silico analysis and genotyped by PCR-restriction fragment length polymorphism (RFLP) followed by bidirectional Sanger sequencing. In addition, the gene expression of NRF2 in patients with polymorphism was analyzed by qPCR to evaluate the functional impact of the SNP.

RESULTS

NRF2 expression was significantly decreased among the T2DM and DFU subjects when compared to the NGT subjects. Of particular interest, the homozygous mutant (TT) genotype of rs182428269 polymorphism was significantly associated with an increased risk for the development of T2DM (OR = 1.95 (1.02-3.72), p = 0.04) and DFU (OR = 5.66 (2.98-10.76), p = 0.0001). Furthermore, a progressive decline in NRF2 expression was observed among the T2DM and DFU subjects with "TT" genotype compared to the "CC" and "CT" genotypes.

CONCLUSION

NRF2 polymorphism rs182428269 is associated with the pathogenesis of T2DM and DFU.

摘要

背景

核因子红细胞 2 相关因子 2（NRF2）在氧化还原平衡和伤口愈合中的关键作用已得到充分证实。然而，调节 2 型糖尿病和糖尿病足溃疡中 NRF2 的遗传机制仍未得到探索。本研究调查了 2 型糖尿病和糖尿病足溃疡患者中 NRF2 单核苷酸多态性 rs182428269（-127C/T）的关联。

方法

本横断面研究包括 400 名参与者，分为三组：I 组：正常糖耐量受试者（NGT，n=150）、II 组：2 型糖尿病患者（T2DM，n=150）和 III 组：感染性糖尿病足溃疡患者（DFU，n=100）。根据计算机分析选择非同义 SNP rs182428269，并通过 PCR-限制性片段长度多态性（RFLP）进行基因分型，然后进行双向 Sanger 测序。此外，通过 qPCR 分析具有多态性的患者的 NRF2 基因表达，以评估 SNP 的功能影响。

结果

与 NGT 受试者相比，T2DM 和 DFU 受试者的 NRF2 表达明显降低。有趣的是，rs182428269 多态性的纯合突变（TT）基因型与 T2DM（OR=1.95（1.02-3.72），p=0.04）和 DFU（OR=5.66（2.98-10.76））的发展风险显著相关，p=0.0001）。此外，与“CC”和“CT”基因型相比，T2DM 和 DFU 受试者中“TT”基因型的 NRF2 表达呈进行性下降。