Intercellular adhesion molecule 1 (ICAM1) Lys56Met and Gly241Arg gene variants, plasma-soluble ICAM1 concentrations, and risk of incident cardiovascular events in 23,014 initially healthy white women

Abstract

Background and purpose: The objective of this study was to examine the association of 2 nonsynonymous intercellular adhesion molecule 1 (ICAM1) gene variants (Lys56Met and Gly241Arg) with baseline plasma soluble ICAM1 concentrations and with risk of total and selected cardiovascular disease (CVD) events in a prospective cohort of 23 014 apparently healthy white American women followed for 10 years. ICAM1 variations have been associated with plasma soluble ICAM1 concentrations and inflammatory conditions, including atherosclerosis. However, to date, no large prospective, genetic-epidemiological data set is available that would allow evaluation of the degree of association of these gene variants with risk of CVD.

Methods: ICAM1 genotypes and baseline plasma soluble ICAM1 concentrations were determined. The primary outcome measure was a composite CVD end point (incident ischemic stroke, myocardial infarction, or death due to ischemic CVD); other measures were incident ischemic stroke, myocardial infarction, and coronary revascularization. During follow-up, 751 total incident CVD events, 187 incident myocardial infarction cases, 203 incident ischemic stroke cases, and 433 coronary revascularization events occurred.

Results: All observed genotype frequencies were in Hardy-Weinberg equilibrium across the whole sample population. We found baseline plasma soluble ICAM1 concentrations to be significantly reduced among carriers of Met56 allele (P<0.0001) and Arg241 allele (P<0.0001) as compared with the respective noncarriers of these variants. However, the polymorphisms tested and the respective haplotypes were neither associated with overall risk nor with risk with risk for selected CVD events regardless of whether analyses were adjusted for traditional CVD risk factors/confounders (all P values >0.10).

Conclusions: In this large prospective study, we found an association of the nonsynonymous gene variants tested with reduced baseline plasma soluble ICAM1 concentrations. However, no evidence was found for an association of the gene variants tested with the overall or selected CVD end points examined, suggesting that these variants may not add useful aids to current risk predictors for early assessment of cardiovascular events.