title: Genotype-specific association between circulating soluble cellular adhesion molecules and carotid intima-media thickness in community residents: J-SHIPP study. Shimanami Health Promoting Program.
abstract: Plasma levels of soluble forms of cellular adhesion molecules (CAMs) and their relationships with carotid intima-media thickness (IMT) were investigated in community residents. Plasma levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured by ELISA in 200 community residents in Japan. Carotid IMT showed a weak but significant positive correlation with the plasma levels of both sICAM-1 (r=0.175, p=0.013) and sVCAM-1 (r=0.19, p=0.0075). Gene polymorphisms of angiotensin converting enzyme (ACE) insertion/deletion (I/D), angiotensinogen (AGT) M235T, angiotensin II type 1 receptor (AT1R) A1166C and apolipoprotein E (apoE) were determined for each subject. The plasma level of sVCAM-1 tended to be lower in subjects with the ACE DD genotype than in those with the ACE ID and II genotypes (373+/-94, 421+/-133, 443+/-135 ng/ml, respectively, p=0.056). However, there were no genotype-specific differences in the plasma levels of soluble forms of CAMs for the other genes examined. In a separate analysis, the plasma level of sICAM-1 was significantly associated with carotid IMT in ACE D carriers (ID + DD) (r=0.28, p=0.002), AGT M carriers (MT + MM) (r=0.32, p=0.0045), and subjects with apoE4 (r=0.35, p=0.036). In contrast, the plasma level of sVCAM-1 showed significant positive correlations with carotid IMT in subjects with the ACE II genotype (r=0.33, p=0.0027) or AGT TT genotype (r= 0.22, p=0.015), and subjects with apoE E2/E3 or E3/E3 (r=0.16, p=0.043). Stepwise regression analysis showed that plasma sVCAM-1 was independently associated with carotid IMT in subjects with the ACE II genotype or apoE4 genotype. Similarly, the plasma level of sICAM-1 was independently associated with carotid IMT in AGT M carriers. These findings suggest that genetic background could be involved in the association between plasma CAMs and atherosclerosis.
authors.affiliation: Department of Geriatric Medicine, Ehime University School of Medicine, Japan. koharak@m.ehime-u.ac.jp
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Kohara
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Tabara
authors.forename: Yoshikuni
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Michiya
authors.initials: M
authors.lastname: Igase
authors.forename: Jun
authors.initials: J
authors.lastname: Nakura
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Miki
mesh_terms: D000368:Aged; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D002339:Carotid Arteries / Q000000981:diagnostic imaging*; D004251:DNA Transposable Elements; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood* / Q000737:chemistry; D008137:Longitudinal Studies; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D012995:Solubility; D017539:Tunica Intima / Q000000981:diagnostic imaging*; D017540:Tunica Media / Q000000981:diagnostic imaging*; D014463:Ultrasonography; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood* / Q000737:chemistry
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D004251:DNA Transposable Elements; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D007703:Peptidyl-Dipeptidase A