Examination of genetic effects of polymorphisms in the MCP-1 and CCR2 genes on MI in the Icelandic population

Bjarnadottir, Kristjana; Eiríksdóttir, Guðný; Aspelund, Thor; Gudnason, Vilmundur

doi:10.1016/j.atherosclerosis.2005.11.014

Cited by 30 publications

(20 citation statements)

References 36 publications

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“…In both studies, age limitation is in agreement with the recent hypothesis that genetic factors may have impact on MI patients with onset only before the age of 65 years 53,54 . In contrast, no association of this SNP with MI was found in Spanish or Icelandic cohorts 18,55 . Additionally, patients with the rare allele CCR2-64I have less coronary artery calcification 56 , but there was no association of the CCR2 genotype with coronary atherosclerosis 53 .…”

Section: Atherosclerosis and MImentioning

confidence: 67%

Polymorphisms in CCL2&CCL5 chemokines/chemokine receptors genes and their association with diseases

Navratilova¹

2006

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Section: Atherosclerosis and MImentioning

confidence: 67%

Polymorphisms in CCL2&CCL5 chemokines/chemokine receptors genes and their association with diseases

Navratilova¹

2006

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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“…20 However, the Val64Ile allele was not associated with MI in a retrospective study of patients in Iceland who survived an MI at 37-69 years of age. 22 Two isoforms of the receptor, CCR2A and CCR2B, are the result of alternative splicing. Using Jurkat T cells transfected with plasmids encoding the human CCR2A or CCR2B gene, Sanders et al 23 observed that MCP-1 bound to both forms with high affinity but a fivefold less MCP-1-induced chemotaxis was noted in CCR2B-expressing cells compared to CCR2A-expressing cells.…”

Section: Discussionmentioning

confidence: 99%

Circulating MCP-1 levels shows linkage to chemokine receptor gene cluster on chromosome 3: the NHLBI Family Heart Study follow-up examination

et al. 2007

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Atherogenesis is a chronic inflammatory process. Critical in the inflammation process is monocyte chemoattractant protein-1 (MCP-1). To locate genomic regions that affect circulating MCP-1 levels, a genome-wide linkage scan was conducted in a sample of whites and blacks. Phenotype and genetic marker data were available for 2501 white and 513 black participants in the National Heart Lung Blood Institute Family Heart Study follow-up examination. Heritability for MCP-1 was 0.37 in whites and 0.47 in blacks after adjusting for the effects of sex, age, age-sex interaction, smoking status, lifetime smoking exposure (pack-years) and field center. Significant linkage was observed for MCP-1 in a combined black and white sample on chromosome 3 (logarithm of the odds ratio (LOD) ¼ 3.5 at 78 cM, P ¼ 0.0001) and suggestive linkage was observed in whites on chromosome 5 (LOD ¼ 1.8 at 128 cM, P ¼ 0.002). Located under the linkage peak on chromosome 3 is the chemokine receptor gene cluster, including CCR2, the receptor for MCP-1. This study provides preliminary evidence linking genetic variation in a receptor to circulating levels of its ligand, as previously demonstrated for the low-density lipoprotein receptor. Further characterization of these chromosomal regions is needed to identify the functional mutations associated with circulating levels of MCP-1.

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“…9,10 In humans, gene variants of MCP-1 and CCR2 have also been reported to increase the susceptibility to CHD in some, 11,12 but not all, studies. 13 Cross-sectional studies investigating circulating chemokine levels suggest that these processes might also be reflected on the systemic level. MCP-1 and IL-8 concentrations have been reported to be associated with traditional cardiovascular risk factors, atherosclerosis, and prevalent CHD.…”

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confidence: 99%

Chemokines and Incident Coronary Heart Disease

Herder

Baumert

Thorand

et al. 2006

ATVB

112

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Objectives-The chemokines monocyte chemoattractant protein-1 (MCP-1/CCL2), interleukin-8 (IL-8/CXCL8), and interferon-␥-inducible protein-10 (IP-10/CXCL10) have been reported to be involved in the development of atherosclerosis and type 2 diabetes. The aim of this study was to assess whether elevated systemic levels of these chemokines precede coronary events. Methods and Results-We investigated MCP-1, IL-8, and IP-10 serum levels in a case-cohort design based on data from 381 individuals (294 men, 87 women) with and 1977 individuals (1006 men, 971 women) without incident coronary heart disease (CHD) from the prospective, population-based MONICA/KORA Augsburg study (1984 to 2002). The mean follow-up time was 11.0 years. Baseline concentrations were significantly higher in cases compared with noncases (PՅ0.001 for all chemokines). MCP-1 and IL-8 remained associated with CHD risk after adjustment for age, sex, and survey with hazard ratios (95% confidence intervals) comparing extreme tertiles of 1.39 (1.05 to 1.84) for MCP-1 and 1.48 (1.10 to 1.99) for IL-8. However, adjustment for further cardiovascular and immunologic risk factors attenuated the observed associations, and they became nonsignificant. Conclusions-Elevated systemic levels of the chemokines MCP-1, IL-8, and IP-10 precede CHD but do not represent independent risk factors. Thus, the associations are less pronounced than previously shown for type 2 diabetes. Key Words: chemokines Ⅲ inflammation Ⅲ coronary heart disease Ⅲ case-cohort study Ⅲ prognosis I nflammatory mechanisms play an important role in the initiation and progression of cardiovascular diseases. 1 Key mediators in these processes are chemokines, a family of low-molecular-weight proteins regulating cell migration to sites of inflammation and triggering activation of many cell types. 2 They have chemotactic properties, and the repertoire of chemokine receptors on the cell surface determines the migration behavior of leukocytes and other cells. Chemokines like monocyte chemoattractant protein-1 (MCP-1/CCL2), interleukin-8 (IL-8/CXCL8), and INF-␥-inducible protein-10 (IP-10/CXCL10) are expressed in atherosclerotic lesions. [3][4][5] Their release by endothelial cells, smooth muscle cells, macrophages, and perivascular adipose tissue has been shown to mediate leukocyte adhesion to endothelial cells as well as infiltration into the arterial wall 6 and presumably also into epicardial fat, with implications for the development of coronary heart disease (CHD). 7,8 There is further evidence from preclinical and clinical studies for a contribution of chemokines to CHD. On the genetic level, deletion of MCP-1/CCL2 or its receptor CCR2 strongly attenuate macrophage recruitment and lesion formation in atherosclerosis-prone mice. 9,10 In humans, gene variants of MCP-1 and CCR2 have also been reported to increase the susceptibility to CHD in some, 11,12 but not all, studies. 13 Cross-sectional studies investigating circulating chemokine levels suggest that these processes might also be reflected on the ...

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Examination of genetic effects of polymorphisms in the MCP-1 and CCR2 genes on MI in the Icelandic population

Cited by 30 publications

References 36 publications

Polymorphisms in CCL2&CCL5 chemokines/chemokine receptors genes and their association with diseases

Polymorphisms in CCL2&CCL5 chemokines/chemokine receptors genes and their association with diseases

Circulating MCP-1 levels shows linkage to chemokine receptor gene cluster on chromosome 3: the NHLBI Family Heart Study follow-up examination

Chemokines and Incident Coronary Heart Disease

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