Intercellular Adhesion Molecule 1 (ICAM-1) Gene Variant Is Associated with Coronary Artery Calcification Independent of Soluble ICAM-1 Levels

Reilly, Muredach P; Wolfe, Megan L.; Dykhouse, Jennifer; Reddy, K Krishna Mohan; Localio, Russell; Rader, Daniel J.

doi:10.1136/jim-52-08-23

Cited by 10 publications

(14 citation statements)

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“…The association of sICAM-1 and CAC did not remain significant in fully-adjusted models of four studies 14–17 . However, these studies were limited by small sample sizes 14,17 , and low sICAM-1 assay precision 16 Tang et al 15 studied 2246 white family members in the NHLBI Family Heart Study, mean age 55 years. Unadjusted or minimally adjusted associations of sICAM-1 with CAC are concordant with our findings, but we could not identify obvious differences between our study and these other studies that would explain why sICAM-1 remained significant after full adjustment in our study.…”

Section: Discussionmentioning

confidence: 79%

“…If a threshold model were correct, another factor that induced exceptionally high sICAM-1 could be important. For example, genetic state could be important, since several SNP variants in the ICAM gene have been associated with elevated sICAM-1 concentration 14, 32–34 .…”

Section: Discussionmentioning

confidence: 99%

“…In children with hypertension and obesity 12 and in familial combined hyperlipidemia pedigrees 13 , sICAM-1 was positively correlated with IMT. Additional studies reported that sICAM-1 was positively associated with the presence of coronary artery calcified plaque (CAC), an established measure of subclinical atherosclerosis and CVD events; however, the association was attenuated after adjusting for traditional cardiovascular risk factors 14–17 . Inconsistencies among these associations may reflect differential pathophysiology indicated by the different subclinical markers.…”

Section: Introductionmentioning

confidence: 99%

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Circulating Soluble Intercellular Adhesion Molecule 1 and Subclinical Atherosclerosis: the Coronary Artery Risk Development in Young Adults Study

Gross¹,

Bielinski²,

Suárez-López

et al. 2012

Clinical Chemistry

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Background Soluble intercellular adhesion molecule-1 (sICAM-1) is associated with endothelial dysfunction and clinical cardiovascular disease. We investigated the relationship of subclinical atherosclerosis with sICAM-1 concentration. Methods sICAM-1 concentration was assayed at year 15 of the Coronary Artery Risk Development in Young Adults (CARDIA) Study (black and white men and women, average age 40 years). We assessed progression of coronary artery calcification through year 20 (CAC, n=2378), and both carotid artery stenosis (n=2432) and intima media thickness at year 20 (IMT, n = 2240). Results Median sICAM-1 was 145.9 ng/ml. Among a subgroup with advanced atherosclerotic plaque (either CAC or stenosis), IMT was 0.010 (95% confidence interval (CI) 0.003–0.017 mm) higher per standard deviation of sICAM-1 (44 ng/ml) in a model adjusted for age, race, sex, clinic, smoking, exercise, body size, education, blood pressure, antihypertensive medication, plasma lipids, and cholesterol lowering medication. With the same adjustment, the odds ratios (OR) for the presence of year 20 carotid artery stenosis per SD of sICAM-1 was 1.12 (CI 1.01–1.25, p<0.04), while for occurrence of CAC progression the OR was 1.16 (CI 1.04–1.31, p<0.01). The associations with CAC and carotid stenosis were strongest in the top 20th of the sICAM-1 distribution. Conclusion sICAM-1 concentration may be an early biomarker that indicates changes in the artery wall that accompany atherosclerosis, as well as the presence of advanced plaque in the coronary and carotid arteries. This finding holds in people with low total burden of atherosclerosis, decades prior to the development of clinical CVD.

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Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Circulating Soluble Intercellular Adhesion Molecule 1 and Subclinical Atherosclerosis: the Coronary Artery Risk Development in Young Adults Study

Gross¹,

Bielinski²,

Suárez-López

et al. 2012

Clinical Chemistry

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“…Several previous studies have found an association with ICAM1 SNPs and cardiovascular disease, albeit inconsistently. In a German case control study, rs5498 was associated with an OR = 2.2 for coronary heart disease 24 , in the Study of Inherited Risk of Coronary Atherosclerosis (SIRCA) this SNP was associated with CAC in men independently of sICAM-1 level 25 , and was associated with a higher risk of restenosis after coronary stenting in Chinese 26 . The rs5498 SNP was also associated with peripheral arterial occlusive disease in an Italian population 27 .…”

Section: Discussionmentioning

confidence: 97%

Polymorphisms in the ICAM1 gene predict circulating soluble intercellular adhesion molecule-1(sICAM-1)

et al. 2011

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Objective Polymorphisms within the ICAM1 structural gene have been shown to influence circulating levels of soluble intercellular adhesion molecule -1 (sICAM-1) but their relation to atherosclerosis has not been clearly established. We sought to determine whether ICAM1 SNPs are associated with circulating sICAM-1 concentration, coronary artery calcium (CAC), and common and internal carotid intima medial thickness (IMT). Methods and Results 3,550 black and white Coronary Artery Risk Development in Young Adults (CARDIA) Study subjects who participated in the year 15 and/or 20 examinations and were part of the Young Adult Longitudinal Study of Antioxidants (YALTA) ancillary study were included in this analysis. In whites, rs5498 was significantly associated with sICAM-1 (p < 0.001) and each G-allele of rs5498 was associated with 5% higher sICAM-1 concentration. In blacks, each C-allele of rs5490 was associated with 6 % higher sICAM-1 level; this SNP was in strong linkage disequilibrium with rs5491, a functional variant. Subclinical measurements of atherosclerosis in either year 15 or year 20 were not significantly related to ICAM1 SNPs. Conclusions In CARDIA, ICAM1 DNA segment variants were associated with sICAM-1 protein level including the novel finding that levels differ by the functional variant rs5491. However, ICAM1 SNPs were not strongly related to either IMT or CAC. Our findings in CARDIA suggest that ICAM1 variants are not major early contributors to subclinical atherosclerosis.

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“…Genome-wide association analysis indicated that ICAM-1 K469E polymorphism had a role in the genetic regulation of sICAM-1 levels [ 29 ]. In addition, Reilly et al found that ICAM-1 K469E EE genotype was associated with lower coronary artery calcification (CAC) scores in men [ 30 ]. Taken together, these data indicate that ICAM-1 K469E polymorphism can influence the risk of CAD.…”

Section: Discussionmentioning

confidence: 99%

Intercellular Adhesion Molecule-1 K469E Polymorphism and Risk of Coronary Artery Disease: A Meta-Analysis

Zou

Pan²,

ZhiGang³

et al. 2014

Med Sci Monit

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BackgroundIntercellular adhesion molecule-1 (ICAM-1) K469E polymorphism has been implicated in susceptibility to coronary artery disease (CAD). Several studies investigated the association of this polymorphism with CAD in different populations but the results were contradictory. A meta-analysis was conducted to assess the association between ICAM-1 K469E polymorphism and CAD susceptibility.Material/MethodsDatabases including PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), and Weipu Database were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. A random-effects model was used.ResultsFifteen case-control studies including 3088 cases and 3466 controls were included. Overall, a significant association between ICAM-1 K469E polymorphism and CAD was observed in the dominant model (OR=1.80; 95% CI 1.62–2.01; P<0.00001; Pheterogeneity=0.40). In subgroup analysis by ethnicity, a significant association was found among Asians (OR=1.92; 95% CI 1.51–2.43; P<0.00001; Pheterogeneity=0.98) and among Caucasians (OR=1.64; 95% CI 1.30–2.08; P<0.0001; Pheterogeneity=0.04). In the subgroup analysis by age, a significant association was found among young patients (OR=1.46; 95% CI 1.10–1.93; P=0.008; Pheterogeneity=0.21) and old patients (OR=1.92; 95% CI 1.75–2.10; P<0.00001; Pheterogeneity=0.99).ConclusionsResults of this meta-analysis suggest that ICAM-1 K469E polymorphism confers a risk factor of CAD.

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Intercellular Adhesion Molecule 1 (ICAM-1) Gene Variant Is Associated with Coronary Artery Calcification Independent of Soluble ICAM-1 Levels

Cited by 10 publications

References 0 publications

Circulating Soluble Intercellular Adhesion Molecule 1 and Subclinical Atherosclerosis: the Coronary Artery Risk Development in Young Adults Study

Circulating Soluble Intercellular Adhesion Molecule 1 and Subclinical Atherosclerosis: the Coronary Artery Risk Development in Young Adults Study

Polymorphisms in the ICAM1 gene predict circulating soluble intercellular adhesion molecule-1(sICAM-1)

Intercellular Adhesion Molecule-1 K469E Polymorphism and Risk of Coronary Artery Disease: A Meta-Analysis

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