Abstract | BACKGROUND AND PURPOSE:
Atherosclerosis is a progressive inflammatory disease and can develop in large arteries such as carotid and femoral arteries or medium-sized muscular arteries of the heart. Previous predominantly experimental studies suggested an important role of chemokines in the development of atherosclerosis. The main aim of this study was to examine potential effect of the CCR5-del32 mutation on systemic inflammation, intima-media thickness in carotid and femoral arteries, and on the indices of cardiovascular disease. METHODS: In the present study, we have examined the association of a common functional 32-bp frameshift deletion mutation in a chemokine receptor (CCR5) in relation to inflammation and atherosclerosis. CCR5 is a G protein-coupled receptor involved in inflammatory response and regulation of leukocytes activation and migration. Genetic screening of this mutation was carried out on a well-known and previously described cohort of Bruneck (n=826) using polymerase chain reaction. RESULTS: Screening was successful in 810 subjects of whom 7 were homozygous, 102 were heterozygous, and 701 were normal. The mutation was associated with significantly lower levels of C-reactive protein in a dose-dependent manner. Moreover, CCR5-del32 was associated with a significantly lower carotid intima-media thickness in the common carotid artery (del32/del32, 837+/-8 microm; wt/del32, 909+/-21 microm; wt/wt, 958+/-8 microm; P=0.007 after multivariable adjustment). Furthermore, incident cardiovascular disease (1995 to 2005) was markedly reduced in del32 homozygotes and heterozygotes subjects compared with wild-type homozygotes (del32/del32=0%, wt/del32=7.8%, wt/wt=14.8%, P=0.020). Findings equally applied to coronary artery and cerebrovascular disease. CONCLUSIONS:
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Authors | Ali R Afzal, Stefan Kiechl, Yousef P Daryani, Arusha Weerasinghe, Yang Zhang, Markus Reindl, Agnes Mayr, Siegfried Weger, Qingbo Xu, Johann Willeit |
Journal | Stroke
(Stroke)
Vol. 39
Issue 7
Pg. 1972-8
(Jul 2008)
ISSN: 1524-4628 [Electronic] United States |
PMID | 18436884
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Receptors, CCR5
- C-Reactive Protein
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Topics |
- Adult
- Aged
- Arteries
(pathology)
- Atherosclerosis
(genetics)
- C-Reactive Protein
(biosynthesis)
- Cardiovascular Diseases
(blood)
- Female
- Frameshift Mutation
- Gene Deletion
- Humans
- Inflammation
(blood, genetics)
- Male
- Middle Aged
- Receptors, CCR5
(genetics, physiology)
- Risk
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