Genotype-Specific Association between Circulating Soluble Cellular Adhesion Molecules and Carotid Intima-Media Thickness in Community Residents: J-SHIPP Study.
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<B>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 (<I>r</I>=0.175, <I>p</I>=0.013) and sVCAM-1 (<I>r</I>=0.19, <I>p</I>=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, <I>p</I>=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) (<I>r</I>=0.28, <I>p</I>=0.002), AGT M carriers (MT + MM) (<I>r</I>=0.32, <I>p</I>=0.0045), and subjects with apoE4 (<I>r</I>=0.35, <I>p</I>=0.036). In contrast, the plasma level of sVCAM-1 showed significant positive correlations with carotid IMT in subjects with the ACE II genotype (<I>r</I>=0.33, <I>p</I>=0.0027) or AGT TT genotype (<I>r</I>=0.22, <I>p</I>=0.015), and subjects with apoE E2⁄E3 or E3⁄E3 (<I>r</I>=0.16, <I>p</I>=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. (<I>Hypertens Res</I> 2002; 25: 31-39)</B>
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