The K469E polymorphism of the intercellular adhesion molecule-1 gene is associated with plasma fibrinogen level in type 2 diabetes.
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.
Yokoyama
Hisayo
H
Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.
Tahara
Hideki
H
Emoto
Masanori
M
Fujiwara
Shigehiko
S
Araki
Takahiro
T
Shinohara
Kayo
K
Hatsuda
Sawako
S
Maeno
Takaaki
T
Shoji
Takuhito
T
Koyama
Hidenori
H
Shoji
Tetsuo
T
Nishizawa
Yoshiki
Y
D000419:Albuminuria; D001794:Blood Pressure; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000000981:diagnostic imaging / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D005263:Femoral Artery / Q000000981:diagnostic imaging; D005340:Fibrinogen / Q000032:analysis*; D005838:Genotype; D006801:Humans; D007333:Insulin Resistance; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D014463:Ultrasonography
D008076:Cholesterol, HDL; D018799:Intercellular Adhesion Molecule-1; D005340:Fibrinogen; D002784:Cholesterol