BACKGROUND AND PURPOSE: If chronic inflammation plays a causal role in atherogenesis, individuals with proinflammatory gene variants would be expected to develop more atherosclerosis. We recently found a synergistic association between 3 functional proinflammatory gene polymorphisms/haplotypes and smoking on carotid intima-media thickness (IMT). We replicated this finding in a second large population and extended the analysis by inclusion of other inflammatory conditions (chronic infection and obesity/abnormal glucose tolerance). METHODS: Common carotid and femoral artery IMT was determined in the Bruneck Study population (n=810). Proinflammatory variants were determined in 3 genes (IL-6 [-174C, -572G, -597A haplotype], IL-1-receptor antagonist [VNTR *2], and endotoxin receptor CD-14 [-159C]). RESULTS: There was a significant relationship between gene-variant score and carotid IMT: age- and sex-adjusted mean IMT in subjects with 0, 1, and >or=2 gene variants was 936, 987 and 1047 microm, respectively (P=0.001), and synergistic effects of gene-variant score and smoking on IMT measurements (P=0.040). Analogous findings were obtained for obesity/abnormal glucose tolerance and chronic infection. Interactive effects of gene-variant score and a risk factor score composed of the acquired inflammatory conditions were highly significant (P<0.001 each). Results were similar for femoral artery IMT. CONCLUSIONS: These results provide support for a causal role of inflammation in carotid atherosclerosis, and emphasize the importance of gene-gene and gene-environment interactions in this pathogenic pathway. This may help to explain the substantial variability of disease expression in subjects with proinflammatory risk factors such as smoking, diabetes and chronic infection.
BACKGROUND AND PURPOSE: If chronic inflammation plays a causal role in atherogenesis, individuals with proinflammatory gene variants would be expected to develop more atherosclerosis. We recently found a synergistic association between 3 functional proinflammatory gene polymorphisms/haplotypes and smoking on carotid intima-media thickness (IMT). We replicated this finding in a second large population and extended the analysis by inclusion of other inflammatory conditions (chronic infection and obesity/abnormal glucose tolerance). METHODS: Common carotid and femoral artery IMT was determined in the Bruneck Study population (n=810). Proinflammatory variants were determined in 3 genes (IL-6 [-174C, -572G, -597A haplotype], IL-1-receptor antagonist [VNTR *2], and endotoxin receptor CD-14 [-159C]). RESULTS: There was a significant relationship between gene-variant score and carotid IMT: age- and sex-adjusted mean IMT in subjects with 0, 1, and >or=2 gene variants was 936, 987 and 1047 microm, respectively (P=0.001), and synergistic effects of gene-variant score and smoking on IMT measurements (P=0.040). Analogous findings were obtained for obesity/abnormal glucose tolerance and chronic infection. Interactive effects of gene-variant score and a risk factor score composed of the acquired inflammatory conditions were highly significant (P<0.001 each). Results were similar for femoral artery IMT. CONCLUSIONS: These results provide support for a causal role of inflammation in carotid atherosclerosis, and emphasize the importance of gene-gene and gene-environment interactions in this pathogenic pathway. This may help to explain the substantial variability of disease expression in subjects with proinflammatory risk factors such as smoking, diabetes and chronic infection.
Authors: Miina K Ohman; Yuechun Shen; Chinyere I Obimba; Andrew P Wright; Mark Warnock; Daniel A Lawrence; Daniel T Eitzman Journal: Circulation Date: 2008-01-22 Impact factor: 29.690
Authors: Peter Willeit; Simon G Thompson; Stefan Agewall; Göran Bergström; Horst Bickel; Alberico L Catapano; Kuo-Liong Chien; Eric de Groot; Jean-Philippe Empana; Thorleif Etgen; Oscar H Franco; Bernhard Iglseder; Stein H Johnsen; Maryam Kavousi; Lars Lind; Jing Liu; Ellisiv B Mathiesen; Giuseppe D Norata; Michael H Olsen; Aikaterini Papagianni; Holger Poppert; Jackie F Price; Ralph L Sacco; David N Yanez; Dong Zhao; Ulf Schminke; Alpaslan Bülbül; Joseph F Polak; Matthias Sitzer; Albert Hofman; Liliana Grigore; Marcus Dörr; Ta-Chen Su; Pierre Ducimetière; Wuxiang Xie; Kimmo Ronkainen; Stefan Kiechl; Tatjana Rundek; Christine Robertson; Björn Fagerberg; Lena Bokemark; Helmuth Steinmetz; M Arfan Ikram; Henry Völzke; Hung-Ju Lin; Matthieu Plichart; Tomi-Pekka Tuomainen; Moise Desvarieux; Stela McLachlan; Caroline Schmidt; Jussi Kauhanen; Johann Willeit; Matthias W Lorenz; Dirk Sander Journal: Eur J Prev Cardiol Date: 2014-11-21 Impact factor: 7.804