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See related articles, pages 1109–1120. Cardiovascular disease (CVD), including coronary artery disease (CAD) with its fatal clinical outcome myocardial infarction (MI) and stroke, remain the leading cause of deaths in western and nonwestern countries.1,2 In the US, CVD claims more lives than cancer, chronic lower respiratory tract diseases and diabetes mellitus combined, accounting for ≈36% of all deaths in 2004 and incurring an estimated direct and indirect cost of ≈432 billion dollars in 2007.2 Stroke and MI are multifactorial traits with complex pathophysiology. Besides other established factors, family history of disease strongly and independently determines CVD risk.3 There is a nearly 5-fold difference in stroke risk between monocygotic and dizygotic twins,4 and with respect to race, stroke incidence is approximately twice as high in blacks compared to whites.5 Marenberg et al,6 in their study on ≈20 000 Swedish twins, demonstrated that the relative risk to die from MI, when the other twin already died from this disease, was twice as large for monozygotic compared to dizygotic twins. Celera Genomics7 and the International Human Genome Project consortium,8 by whole genome shotgun and clone-based sequencing strategies, respectively, proposed 2 versions of the human genome—the diploid genome offering more genetic information than previously anticipated.9 The availability of almost the entire human genome sequence allows for the immediate access to specific target sequences across the human genome. The number of different technologies to explore genetic sequences on a “genome-wide” scale and high-throughput genotyping methods is steadily increasing. Genome-wide approaches are essentially based on the fact that alleles at nearby loci often show strong linkage disequilibrium (LD). Human recombination events occur ubiquitously in short genomic hotspots (1 to 2 kb) every 100 to 200 kb, preferentially outside genes,10 leading to a breakdown of allelic …

Background and Purpose— Carotid intima-media thickness (IMT) reflects generalized atherosclerosis and is predictive of future vascular events. Evidence exists that carotid IMT is heritable, and genetic studies can provide clues in the pathogenesis of atherosclerosis. Methods— We recruited 470 white ischemic stroke patients, measured common carotid artery (CCA) IMT, and analyzed 54 polymorphisms with suspected roles in atherosclerosis. Results— Among the polymorphisms tested, the angiotensin-converting enzyme insertion/deletion, osteopontin (OPN) T-443C, monocyte chemoattractant protein-1 (MCP-1) G-927C, and MCP-1 A-2578G polymorphisms were associated with CCA–IMT in age-gender–adjusted analysis. In multivariate analysis, the association between the OPN and MCP-1 polymorphisms remained significant. The OPN-443C allele was associated with increased IMT in the dominant model (0.053 mm for the TC and CC genotypes; P =0.001). The MCP-1-927C allele was associated with increased IMT in the additive model (0.040 mm for each C allele; P =0.001), and the MCP-1-2578 G allele was associated with decreased IMT in the recessive model (0.088 mm for the GG genotype; P =0.002). Conclusions— The OPN and MCP-1 genes, coding for 2 cytokines with known roles in atherosclerosis, may contribute to increased carotid IMT and warrant further study.