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

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.

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Role of engulfment and cell motility 1 (ELMO1) gene polymorphism in development of diabetic kidney disease

Egyptian Journal of Medical Human Genetics ◽

10.1186/s43042-021-00167-8 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Thoria A. Omar ◽

Shimaa K. Zewain ◽

Mohamed M. Ghonaim ◽

Khadija A. Refaat ◽

Dalia H. Abou-Elela

Keyword(s):

Kidney Disease ◽

Gene Polymorphism ◽

Cell Motility ◽

Diabetic Kidney Disease ◽

Association Studies ◽

Diabetic Patients ◽

Genome Wide Association Studies ◽

Diabetic Kidney ◽

Genotype Frequencies ◽

Significant Difference

Abstract Background Diabetic kidney disease (DKD) is a progressive kidney disease that affects diabetic patients irrespective of glycemic state or hypertension. Therefore, early detection of DKD is of critical importance. Many genome-wide association studies have identified the engulfment and cell motility 1 (ELMO1) gene as a genetic marker linked to DKD. This study aimed to investigate the association between ELMO1 rs741301 gene polymorphism and the development of DKD among Egyptian patients with type 2 diabetes mellitus (T2DM). Allele and genotype frequencies were investigated in 304 subjects by real-time PCR allelic discrimination assay: 100 DKD patients, 102 diabetic patients without DKD, and 102 healthy controls. Results GG genotype of ELMO1 (rs741301) SNP and its allele frequencies were significantly high in all diabetic patients. GG genotype had an odds ratio (OR) of 6.095 and 95% confidence interval (CI) of 2.456–15.125, p < 0.001, while the frequent allele G had an OR of 2.366 and 95% CI of 1.450–3.859, p = 0.001. No significant difference was observed between T2DM without DKD and DKD. Conclusion Our results could not establish an association between the ELMO1 rs741301 variant and the progression of DKD.

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The Association of a Genetic Variant inSCAF8-CNKSR3with Diabetic Kidney Disease and Diabetic Retinopathy in a Chinese Population

Journal of Diabetes Research ◽

10.1155/2017/6542689 ◽

2017 ◽

Vol 2017 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

Li Jin ◽

Tao Wang ◽

Song Jiang ◽

Miao Chen ◽

Rong Zhang ◽

...

Keyword(s):

Type 2 Diabetes ◽

Diabetic Retinopathy ◽

Kidney Disease ◽

Mexican Americans ◽

Diabetic Kidney Disease ◽

Association Studies ◽

Genome Wide Association Studies ◽

Diabetic Kidney ◽

Diabetes Patients

Background. Genome-wide association studies found rs955333 located in 6q25.2 was associated with diabetic kidney disease in multiple ethnic populations, including European Americans, African Americans, and Mexican Americans. We aimed to investigate the association between the variant rs955333 inSCAF8-CNKSR3and DKD susceptibility in Chinese type 2 diabetes patients.Methods. The variant rs955333 was genotyped in 1884 Chinese type 2 diabetes patients. Associations of the variant rs955333 with DKD and DR susceptibility and related quantitative traits were evaluated.Results. The variant rs955333 was not associated with DKD in our samples, while subjects with genotype GG were associated with DR (P=0.047, OR = 0.55250.308,0.9911), and it also showed association with microalbuminuria (P=0.024, beta = −0.1812-0.339,-0.024).Conclusion. Our data suggests the variant rs955333 was not associated with DKD but showed association with diabetic retinopathy in Chinese type 2 diabetes patients.

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