Genetic, epigenetic and protein analyses of intercellular adhesion molecule 1 in Malaysian subjects with type 2 diabetes and diabetic nephropathy

• Published in: Journal of diabetes and its complications Vol. 29; no. 8; pp. 1234 - 1239
• Main Authors: Abu Seman, Norhashimah, Anderstam, Björn, Wan Mohamud, Wan Nazaimoon, Östenson, Claes-Göran, Brismar, Kerstin, Gu, Harvest F.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2015; Elsevier Limited
• Subjects: Adult; Aged; Amino Acid Substitution; Body mass index; Cohort Studies; Diabetes Mellitus, Type 2 - complications; Diabetic Nephropathies - blood; Diabetic Nephropathies - genetics; Diabetic Nephropathies - metabolism; Diabetic nephropathy; DNA Methylation; Endocrinology & Metabolism; Epigenesis, Genetic; Female; Genetic Association Studies; Genetic Predisposition to Disease; Glucose; Glycated Hemoglobin A - analysis; Humans; Intercellular adhesion molecule 1; Intercellular Adhesion Molecule-1 - blood; Intercellular Adhesion Molecule-1 - genetics; Intercellular Adhesion Molecule-1 - metabolism; Laboratories; Malaysia; Male; Middle Aged; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Single nucleotide polymorphism; Type 2 diabetes; Up-Regulation; Malaysia; Type 2 diabetes; DNA methylation; Diabetic nephropathy; Single nucleotide polymorphism; Intercellular adhesion molecule 1
• ISSN: 1056-8727; 1873-460X
• DOI: 10.1016/j.jdiacomp.2015.07.004

Recent research has implicated that the inflammation may be a key pathophysiological mechanism in diabetic nephropathy (DN). Intercellular adhesion molecule 1 (ICAM-1) is an acute phase marker of inflammation. In the present study, we carried out genetic, epigenetic and protein analyses of ICAM-1 in a Malaysian population, including normal glucose tolerance (NGT) subjects and type 2 diabetes (T2D) patients with or without DN in order to evaluate its role in DN. Analyses of DNA polymorphism and methylation in the ICAM1 gene were performed with TaqMan allelic discrimination and pyrosequencing, respectively. Plasma ICAM-1 levels were determined using an enzyme-linked immune-sorbent assay kit. We found that the ICAM1 K469E(A/G) polymorphism (rs5498) was significantly associated with DN. Particularly, 86.1% of T2D patients with DN carried heterozygous genotype compared to the patients without DN (68.6%). Furthermore, plasma ICAM-1 levels were increased from NGT subjects to T2D patients without and with DN (P<0.001). The NGT subjects carrying heterozygous genotype had significantly lower plasma ICAM-1 levels compared to the K469(A/A) genotype carriers (P=0.009). In the ICAM1 gene promoter, DNA methylation levels of CpG sites were low, and no association of the ICAM1 DNA methylation alteration with DN was detected. The present study provided evidence that the ICAM1 K469E(A/G) polymorphism with high heterozygous index and elevation of plasma ICAM-1 levels were associated with DN in a Malaysian population. Further prospective study of ICAM-1 protein according to the ICAM1 K469E(A/G) genotypes is necessary for predicting the susceptibility to T2D and DN.