P-143: Genotype specific association between circulating soluble cellular adhesion molecules and carotid intima-media thickness in community dwelling healthy residents in Japan

Adhesion molecules play pivotal roles in atherosclerosis. Several studies indicate plasma levels of soluble forms of cellular adhesion molecules (sCAM) could be indices for atherosclerosis including carotid atherosclerosis. To elucidate genetic involvement, the association between plasma levels of sCAM and polymorphism of genes encoding renin-angiotensin system as well as apolipoprotein E (ApoE) was investigated. Carotid intima-media thickness (IMT) and plasma levels of intercellular adhesion molecule-1 (sICAM-1) and vascular adhesion molecule-1 (sVCAM-1) were determined in 200 community dwelling healthy residents free from any medication. Carotid IMT showed a weak but a significant positive correlation with plasma levels of sICAM-1 (r=0.175, p=0.013) as well as sVCAM-1 (r=0.19, p=0.0075). Gene polymorphisms of ACE I/D, angiotensinogen (AGT) M235T, angiotensin type 1 receptor (AT1R) A1166C and ApoE were determined for each subjects. Plasma levels of sVCAM-1 tended to be lower in subjects with ACE DD genotype compared with those with ACE ID and II genotypes (373±94, 421±133, 443±135 ng/ml, p=0.056). However, there were no genotype specific differences in plasma levels of sCAM in other genes examined. In a separate analysis, it was revealed that plasma levels of sICAM-1 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 (E2/E4+E3/E4) (r=0.32, p=0.048). On the contrary, plasma levels of sVCAM-1 showed significant positive correlation with carotid IMT in subjects with ACE II genotype (r=0.33, p=0.0027), AGT TT genotype (r=0.22, p=0.015), and subjects with apoE2/E3+apoE3/E3 (r=0.16, p=0.043). Stepwise regression analysis revealed that plasma sVCAM-1 independently associated with carotid IMT in subjects with ACE II genotype and apoE4 genotype. Similarly, plasma levels of sICAM-1 independently associated with carotid IMT in AGT M carriers. These findings indicate that genetic background could be involved in the interaction between sCAMs and atherosclerosis.