Journal of Diabetes Research (Jan 2020)

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

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

DOI
https://doi.org/10.1155/2020/8305460
Journal volume & issue
Vol. 2020

Abstract

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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.