Association between Gly241Arg ICAM-1 gene polymorphism and serum sICAM-1 concentration in the Stanislas cohort

Abstract

Intracellular adhesion molecule-1 (ICAM-1), a cellular adhesion molecule that mediates the interaction of activated endothelial cells with leukocytes, is involved in various inflammatory and cardiovascular disorders. The relation between these markers and genetic polymorphism, however, remains to be elucidated. The aim of this study is to estimate the effect of a single-base polymorphism at codon 241 in exon 4 of ICAM-1 gene on serum sICAM-1 concentration in a healthy population, taking into account other biological determinants of sICAM-1 level. Serum sICAM-1 levels and the G/R241 polymorphism of the ICAM-1 gene were measured in a large healthy population consisting of 413 children aged 6-21 years and 363 adults aged 38-55 years extracted from the Stanislas cohort. The R241 allele was significantly associated with lower sICAM-1 levels and explained 3.4 and 1.9% of the sICAM-1 variability in children and adults, respectively. A codominant pattern contributed better to the model after adjustment for covariates as the RR homozygote effect was higher than that of the GR heterozygote. Moreover, significant independent associations were found between sICAM-1 and smoking, insulin resistance index (HOMA IR), interleukin-6 level, and alkaline phosphatase and aspartate aminotransferase activities. In conclusion, this study revealed a significant association between the G/R241 ICAM-1 polymorphism and serum sICAM-1 levels, probably due to the impairment in binding of ICAM-1 to leukocyte integrin Mac-1 protein.

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

“…20,22,23 To the best of our knowledge, the present study is the first to demonstrate a significant association of the Lys56Met variant with reduced plasma sICAM1 concentrations. However, as noted by others, 20 the observed association of the variants tested with reduced plasma sICAM1 concentrations may be due to linkage disequilibrium with other (nonsynonymous or functional) genetic polymorphism(s) that affect sICAM1 concentrations.…”

“…20,22,23 To the best of our knowledge, the present study is the first to demonstrate a significant association of the Lys56Met variant with reduced plasma sICAM1 concentrations. However, as noted by others, 20 the observed association of the variants tested with reduced plasma sICAM1 concentrations may be due to linkage disequilibrium with other (nonsynonymous or functional) genetic polymorphism(s) that affect sICAM1 concentrations. Of note, the Lys469Glu variant in exon 6 (not tested in the present investigation) was previously shown to be in linkage disequilibrium with the Gly241Arg variant and associated with reduced plasma sICAM1 concentrations 19 ; however, the potential involvement of the Lys469Glu variant in vascular disease remains unclear.…”

“…This domain is of importance for binding to the leukocyte integrin Mac-1. 20 It has been hypothesized that a combination of Lys56Met and Gly241Arg variants affecting the immunoglobulin domains 1 and 3, respectively, of the ICAM1 protein molecule may influence the inflammatory/immune response to inflammatory conditions, including CVD. However, our present study provides no support for this hypothesis from the standpoint of clinically observable associations between genotype and cardiovascular outcome.…”

Genetic susceptibility to progressive massive fibrosis in coal miners

“…ICAM-1 has been shown to play a critical role in bleomycin-induced pulmonary fibrosis by regulating the production of pro-inflammatory cytokines including IL-6 [28]. A polymorphism in codon +241 (A allele) was found to be associated with a lower serum ICAM-1 level and chronic inflammatory diseases [29,30]. IL-6 also plays multiple roles in angiogenesis and vascular remodelling by upregulating VEGF, a major regulator of angiogenesis, in both transcription and protein levels in many cell types [31].…”

A pharmacogenetic analysis of the Canadian Cancer Trials Group MY.10 clinical trial of maintenance therapy for multiple myeloma

“…Minor (C) allele correlates with low ICAM1 levels. 24 Thalidomide is able to downregulate ICAM1. 25 High ICAM1 levels would normally lead to CAMDR and melphalan resistance.…”