C/T polymorphism of the intercellular adhesion molecule-1 gene (exon 6, codon 469). A risk factor for coronary heart disease and myocardial infarction

Jiang, Hong; Klein, Rolf Michael; Niederacher, Dieter; Du, Min; Marx, R.; Horlitz, M; Boerrigter, Guido; Lapp, Harald; Scheffold, Thomas; Krakau, Ingo; Gülker, H

doi:10.1016/s0167-5273(02)00138-9

Cited by 53 publications

(47 citation statements)

References 25 publications

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“…25,[37][38][39][40] When we studied the effect of polymorphisms in factors upstream in the regulatory pathway of the cytokines and acute phase proteins, evidence for an association between genotype at the TNF-238G/A polymorphism and IL-6 was found by ANOVA (Pϭ0.02; Table 5). This association was confirmed using the sib-pair-based analysis (QTDT, 2 ϭ5.7 [1 df]; Pϭ0.02) performed using the genetic model by Fulker et al, 35 which takes possible population stratification into account.…”

Section: Resultsmentioning

confidence: 99%

Genetic Influence on Inflammation Variables in the Elderly

Maat

Bladbjerg

Hjelmborg

et al. 2004

ATVB

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Background-Inflammation variables (C-reactive protein [CRP], fibrinogen, and soluble intercellular adhesion molecule-1[sICAM-1]) have been identified as risk factors for cardiovascular disease. It is still not known how much the regulation of inflammatory risk factors is determined by genetic factors, and the aim of this study was to determine the heritability of these inflammation variables and of the acute phase regulating cytokines interleukin-6 (IL-6) and tumor necrosis factor-␣ (TNF-␣) at older ages. Methods and Results-The heritability of CRP, fibrinogen, sICAM-1, IL-6, and TNF-␣ was determined in a twin study consisting of 129 monozygotic twin pairs and 153 dizygotic same-sex twins aged 73 to 94 years who participated in the Longitudinal Study of Aging of Danish Twins. Furthermore, we determined the influence of selected genetic polymorphisms on the plasma level variations. Genetic factors accounted for 20% to 55% of the variation in plasma levels of the inflammation variables. The highest heritability was found for sICAM-1. The genetic polymorphisms we studied explained only a small, insignificant part of the heritability. Conclusions-This study in elderly twins provides evidence for a substantial genetic component of inflammatory cardiovascular risk factors among the elderly.

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Section: Resultsmentioning

confidence: 99%

Genetic Influence on Inflammation Variables in the Elderly

Maat

Bladbjerg

Hjelmborg

et al. 2004

ATVB

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“…Variation in genes coding for inflammatory cytokines might be associated with risk of inflammatory disease and atherosclerosis. [15][16][17][18] However, studies assessing the impact of variation at inflammatory genes on risk of PE are sparse. 19 -22 The aim of this study was to compare baseline and, prospectively, short-term pregnancy-induced changes in plasma inflammatory markers in women who experienced healthy pregnancies with those whose pregnancy was complicated by PE.…”

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confidence: 99%

Short- and Long-Term Changes in Plasma Inflammatory Markers Associated With Preeclampsia

et al. 2004

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Abstract-Preeclampsia is characterized by hypertension, dyslipidemia, and increased systemic inflammatory response and has been associated with an increased maternal risk of cardiovascular disease later in life. Low-grade chronic inflammation is a risk factor for cardiovascular disease. This study examined changes in inflammatory markers prospectively during pregnancy, the current inflammatory status of women who had a pregnancy complicated by preeclampsia 20 years previously against matched controls, and the association between inflammatory genes and risk of preeclampsia in a case (nϭ106) control (nϭ212) study. In control pregnancies (nϭ34), mean interleukin-10 (IL-10) levels increased 38% (Pϭ0.012) and tumor necrosis factor-␣ (TNF-␣) by 33% (Pϭ0.024) between the first and third trimesters. The mean preeclampsia group IL-10 and TNF-␣ rose by 43% (Pϭ0.013 and Pϭ0.0065, respectively) from the first to the third trimester. In women with preeclampsia only, plasma IL-6 increased from the first to the third trimester ( with a healthy index pregnancy 20 years previously, that persisted after adjustment for smoking and current body mass index. The IL-1␤ (C-511T), IL-6 (G-174C), TNF-␣ (G-308A), E-selectin (S128R), intercellular adhesion molecule-1 (K469E), and C-reactive protein (C1059G) polymorphisms were not associated with risk of developing preeclampsia.In conclusion, preeclampsia is associated with short-and long-term changes in inflammatory status.

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“…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. Although this variant was identified as risk factor for coronary heart disease and myocardial infarction in a German sample population, 24 and for peripheral arterial occlusive disease in an Italian sample popula- tion, 25 it was found not to be associated with ischemic heart disease in a family-based study. 26 Prior studies have included simultaneous measurements of ICAM1 genotypes and plasma sICAM1 concentrations in relation to inflammatory conditions, but no study has as yet evaluated associations with actual atherothrombotic events, and none was conducted in a large, prospective setting.…”

Section: Discussionmentioning

confidence: 83%

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

Zee

Cheng

Erlich

et al. 2007

Stroke

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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 (PϽ0.0001) and Arg241 allele (PϽ0.0001) 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 Ͼ0.10). 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.

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C/T polymorphism of the intercellular adhesion molecule-1 gene (exon 6, codon 469). A risk factor for coronary heart disease and myocardial infarction

Cited by 53 publications

References 25 publications

Genetic Influence on Inflammation Variables in the Elderly

Genetic Influence on Inflammation Variables in the Elderly

Short- and Long-Term Changes in Plasma Inflammatory Markers Associated With Preeclampsia

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

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