Genetic and Biological Effects of ICAM-1 E469K Polymorphism in Diabetic Kidney Disease.

Xiuli Zhang,Henrik Falhammar,Kerstin Brismar,Harvest F Gu,Norhashimah Abu Seman

doi:10.1155/2020/8305460

Abstract

Diabetic kidney disease (DKD) is a complex disease, in which local inflammatory stress results from both metabolic and hemodynamic derangements. Intercellular adhesion molecule 1 (ICAM-1) is an acute-phase protein marker of inflammation. In the recent years, clinical observations have reported that increased serum/plasma ICAM-1 levels are positively correlated with albuminuria in the patients with type 1 (T1D) and type 2 diabetes (T2D). Genetic association studies have demonstrated that genetic polymorphisms, including SNP rs5498 (E469K, G/A), in the ICAM1 gene is associated with DKD. rs5498 is a nonsynonymous SNP and caused by substitution between E (Glu) and K (Lys) for ICAM-1 protein. In this review, we first summarized the genetic effects of ICAM1 E469K polymorphism in DKD and then demonstrated the possible changes of ICAM-1 protein crystal structures according to the genotypes of this polymorphism. Finally, we discussed the genetic effects of the ICAM1 E469K polymorphism and the biological role of increased circulating ICAM-1 protein and its formation changes in DKD.

Highlights

Diabetes has become a global epidemic and a large proportion of diabetes patients develop microvascular complications
We focused on the evaluation of the genetic effects of the ICAM1 E469K polymorphism in Diabetic kidney disease (DKD) and demonstrated the possible biological changes of Intercellular adhesion molecule 1 (ICAM-1) protein crystal structure according to the genotypes of this polymorphism
We summarized the genetic and biological effects of the ICAM1 E469K polymorphism in DKD, which may provide useful information for better understanding the pathophysiology of the disease

Summary

Introduction

Diabetes has become a global epidemic and a large proportion of diabetes patients develop microvascular complications. We focused on the evaluation of the genetic effects of the ICAM1 E469K polymorphism in DKD and demonstrated the possible biological changes of ICAM-1 protein crystal structure according to the genotypes of this polymorphism. About 10 years later, we replicated the genetic association study of the ICAM1 gene in Malays T2D subjects with or without DKD, and the genotyping experiments were done by using TaqMan allelic discrimination.

Results

Conclusion