The K469E polymorphism of the intercellular adhesion molecule-1 gene is associated with plasma fibrinogen level in type 2 diabetes

Metabolism. 2005 Mar;54(3):381-6. doi: 10.1016/j.metabol.2004.10.002.

Abstract

Intercellular adhesion molecule-1 (ICAM-1) is involved in inflammation and development of atherosclerotic change of vascular endothelium. The aim of the present study is to investigate whether K469E polymorphism of the ICAM-1 gene is associated with various clinical factors including plasma fibrinogen in patients with type 2 diabetes. ICAM-1 gene polymorphism was examined using polymerase chain reaction and restriction enzyme analysis in 360 type 2 diabetic patients. Plasma fibrinogen levels and other clinical variables were measured as well as circulating soluble ICAM-1 (sICAM-1) levels by enzyme-linked immunosorbent assay. The distribution of ICAM-1 genotypes, EE, EK, and KK, was not significantly different between type 2 diabetes and 152 healthy control subjects. Among 3 groups according to ICAM-1 genotypes in type 2 diabetes, no difference was found in adiposity, glycemic control, lipid profile, insulin sensitivity evaluated by homeostasis model assessment, or sICAM-1. Regarding fibrinogen, the patients with E allele showed significantly lower plasma fibrinogen levels in a dose-dependent manner (P = .033). Spearman rank correlation analyses revealed that ICAM-1 genotype showed significant correlation with plasma fibrinogen level (P < .001). In multiple regression analysis, ICAM-1 genotype was independent contribution factor of plasma fibrinogen level as well as high-density lipoprotein-cholesterol and urinary albumin excretion (R2 = 0.148, P < .001). In conclusion, K469E polymorphism of the ICAM-1 gene had impact on plasma fibrinogen level independently of other clinical factors in 360 type 2 diabetic patients, suggesting that fibrinogen is a candidate which links the ICAM-1 gene polymorphism to atherosclerosis.

MeSH terms

  • Albuminuria
  • Blood Pressure
  • Carotid Arteries / diagnostic imaging
  • Cholesterol / blood
  • Cholesterol, HDL / blood
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / diagnostic imaging
  • Diabetes Mellitus, Type 2 / genetics*
  • Exons / genetics
  • Female
  • Femoral Artery / diagnostic imaging
  • Fibrinogen / analysis*
  • Genotype
  • Humans
  • Insulin Resistance
  • Intercellular Adhesion Molecule-1 / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Regression Analysis
  • Ultrasonography

Substances

  • Cholesterol, HDL
  • Intercellular Adhesion Molecule-1
  • Fibrinogen
  • Cholesterol