['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).', '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]).', '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.'] Are genetic and acquired inflammatory conditions synergistically associated with early carotid atherosclerosis?