Coronary Artery Disease-Related Genetic Variant on Chromosome 10q11 Is Associated With Carotid Intima-Media Thickness and Atherosclerosis

Objective-To investigate whether chromosome 10q11.21 influences common carotid intima-media thickness (IMT) and atherosclerosis and whether it is associated with stromal cell-derived factor-1 alpha (SDF-1 alpha) plasma levels. Methods and Results-Variation on chromosome 10q11.21 has been consistently associated with coronary artery disease. The genetic variant lies upstream of the gene encoding SDF-1 alpha. We genotyped 3 population cohorts (Bruneck [age range, 45 to 94 years; 50.0% men; n = 738], Health2000 [age range, 46 to 76 years; 55.4% men; n = 1237], and essential hypertension in families collected in the region of Oxford [HTO] [age range, 19 to 88 years; 47.9% men; n = 770]) for single-nucleotide polymorphism rs501120 at the 10q11.21 locus and conducted a meta-analysis in these cohorts to ascertain a relationship between the polymorphism and carotid IMT. The analysis showed that individuals with the T/T genotype had a significantly higher carotid IMT than individuals with the C/T or C/C genotype (pooled weighted mean difference, 23 mu m [95% CI, 9 to 37 mu m], P = 0.0014 under a fixed-effects model; and 23 mu m [95% CI, 6 to 41 mu m], P = 0.009 under a random-effects model). In the Bruneck cohort, in which data for carotid atherosclerosis and plasma SDF-1 alpha levels were available, we observed an association of the T/T genotype with a higher burden of atherosclerosis and increased susceptibility to the development of atherosclerosis during a 5-year follow-up (multivariable odds ratio, 1.73 [95% CI, 1.18 to 2.52]; P = 0.005 for the recessive model) and an association between the T/T genotype and lower SDF-1 alpha levels (2.62 ng/mL for T/T versus 2.74 ng/mL for C/C or C/T; P = 0.023). Conclusion-The coronary heart disease-related variant at the 10q11.21 locus is associated with carotid IMT and atherosclerosis. (Arterioscler Thromb Vasc Biol. 2010;30:2678-2683.)