K469E polymorphism of the intercellular adhesion molecule-1 gene in Egyptians with coronary heart disease

Abstract

BACKGROUND AND OBJECTIVES:The initial step in atherosclerosis is the adhesion of leukocytes to activated endothelial cells mediated by intercellular adhesion molecule-1 (ICAM-1). This study aimed to investigate the association of K469E polymorphism of the ICAM-1 gene and soluble ICAM-1 (sICAM-1) serum level with coronary heart disease (CHD) in Egyptian subjects.PATIENTS AND METHODS:Using a case-control design, we studied 100 patients with CHD, including 73 patients with acute myocardial infarction (MI) and 27 with unstable angina (UA). The control group consisted of 50 healthy subjects with normal left ventricular function. All participants were genotyped for the ICAM-1 polymorphism by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Serum sICAM-1 was measured by enzyme-linked immunoassay (ELISA).RESULTS:In CHD patients, the frequencies of K genotype (KK and EK) were significantly higher when compared to controls (P<.001) and were associated with an increased risk of disease development (OR=3.8, 95% CI: 1.7 to 8.5; P=.001). K genotype frequencies in patients with MI showed no significant difference when compared to patients with UA (P= .121). Serum sICAM-1 levels were comparable between CHD patients and controls (P= .37) and between MI and UA patients (P=.23). There were no significant differences in sICAM-1 levels among patients with different genotypes (P=.532). Men presented with higher sICAM-1 levels than women (P=.004).CONCLUSION:ICAM-1 gene polymorphism in codon 469 is associated with a risk for CHD development in Egyptian subjects. Serum sICAM-1 is not influenced by this polymorphism and is not necessarily elevated in CHD.

Association of intercellular adhesion molecule-1 gene polymorphism with coronary heart disease

“…Lu et al (17) used nested PCR with allele-specific oligonucleotide primers in 160 patients with CHD and 64 control subjects and found that the A allele frequency and plasma levels of ICAM-1 were higher in patients with CHD than those in control subjects. It was also found that the frequency of the A genotype (AG and GG) was significantly higher in patients with CHD than that in controls in the Egyptian population (18). However, McGlinchey et al (19) found that rs5498 was not associated with ischemic heart disease in Irish populations.…”

The intercellular adhesion molecule-1 (ICAM-1) gene polymorphism K469E in end-stage renal disease patients with cardiovascular disease

“…The frequencies of KK and EK genotypes in patients with MI showed no significant difference compared to patients with unstable angina [18].…”

“…The single nucleotide C to T polymorphism in the sixth exon of the ICAM-1 gene (K469E) results in an amino acid substitution from glutamic acid (E) to lysine (K) in immunoglobulin-like domain 5 of the ICAM-1 protein. This polymorphism has been reported to be involved in inflammatory diseases and atherosclerosis [15][16][17][18].…”

Associations of intercellular adhesion molecule‐1 rs5498 polymorphism with ischemic stroke: A meta‐analysis

“…There are several points that worth noting about this meta‐analysis. First, the rs5498 polymorphism causes an amino acid change from glutamic acid (E) to lysine (K), which is proved to be associated with alteration in protein structure and binding affinity of ICAM‐1 protein (He et al, ; Mohamed et al, ). Thus, it is possible that rs5498 polymorphism may impact biological function of ICAM‐1, give rise to the development of over‐activated inflammatory reactions, and ultimately influence individual susceptibility to IS.…”