Interactions between rs5498 polymorphism in the ICAM1 gene and traditional risk factors influence susceptibility to coronary artery disease

Abstract

Coronary artery disease (CAD) depends on multiple genetic and environmental factors. Adhesion molecules are markers of endothelium dysfunction. Intercellular adhesion molecule-1 (ICAM-1) interacts with leukocyte integrins and promotes atherosclerotic process at the surface of endothelial cells. The aim of the study was to assess the association between ICAM1 rs5498 polymorphism and CAD and to establish whether there are any interactions between this polymorphism and traditional risk factors in determining the risk of CAD. We studied 191 cases with angiographically documented CAD and 203 controls with no signs of cardiovascular diseases. The ICAM1 polymorphism was genotyped using PCR-RFLP method. Data were analyzed with the STATISTICA 7.1 and EpiInfo 6 softwares. We did not observe significant differences in the distribution of genotypes and alleles of rs5498 between cases and controls. We only found a tendency to a higher prevalence of G allele carriers (AG + GG) in patients compared to controls (68 vs. 64%, P = 0.399). A synergistic effect of G allele carrier-state and smoking that had influenced the risk of CAD [synergy index multiplicative (SIM = 2.09)] was observed. Smoking carriers of G allele compared to non-smoking AA were more prevalent in CAD group (39.8%) than among controls (13.3%, P < 0.0001, OR 4.81). Moreover, there was also a synergistic effect between G allele carrier-state and an elevated level of triacylglycerols (TG) (SIM = 1.28) increasing the risk of CAD. There is a synergistic interaction between rs5498 genotype and smoking that increases the risk of CAD.

Interaction of Intercellular Adhesion Molecule 1 (ICAM1) Polymorphisms and Environmental Tobacco Smoke on Childhood Asthma

“…However, Grigg et al found that the soluble ICAM1 level of bronchoalveolar lavage was markedly higher in children whose parents smoked than in those whose parents did not [37]. Sarecka-Hujar et al reported a synergistic interaction between the rs5498 genotype and smoking that affected the risk of coronary artery disease [38]. All of these results support the present findings.…”

Impact of Intercellular Adhesion Molecule-1 Genetic Polymorphisms on Coronary Artery Disease Susceptibility in Taiwanese Subjects

“…Nevertheless, our study could not reveal an association of ICAM-1 rs5498 with CAD significantly. In agreement with this finding, no significant difference was also observed in the distribution of rs5498 genotypes in ICAM-1 gene between cases and controls by another study 26. A number of SNPs may be silent with no direct effect on gene products.…”

Lower Hydrogen Sulfide Is Associated with Cardiovascular Mortality, Which Involves cPKCβII/Akt Pathway in Chronic Hemodialysis Patients

“…Cybulsky [39] and colleagues also found that deficiency of VCAM-1 significantly diminishes early foam cell lesion formation throughout the aorta of Ldlr -/-mice. ICAM-1 has a similar structure, function, and expression patterns with VCAM-1; it plays a pivotal role in lymphocyte migration and activation and is considered important in the pathogenesis of atherosclerosis by compensate for VCAM-1 or cooperate with it in various inflammatory conditions [40] . The mechanisms of the proinflammatory effects of ICAM-1 on endothelial cells might be that ICAM-1 binds and interacts with leukocyte integrin receptors such as lymphocyte function-associated antigen-1 LFA-1 and Mac-1 [41] .…”