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

Lookup NU author(s): Hannah Watkins, Professor Bernard Keavney

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Abstract

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.)

Publication metadata

Author(s): Kiechl S, Laxton RC, Xiao QZ, Hernesniemi JA, Raitakari OT, Kahonen M, Mayosi BM, Jula A, Moilanen L, Willeit J, Watkins H, Samani NJ, Lehtimaki TJ, Keavney B, Xu QB, Ye S

Publication type: Article

Publication status: Published

Journal: Arteriosclerosis, Thrombosis, and Vascular Biology

Year: 2010

Volume: 30

Issue: 12

Pages: 2678-U636

Print publication date: 01/12/2010

ISSN (print): 1079-5642

ISSN (electronic): 1524-4636

Publisher: Lippincott Williams & Wilkins

URL: http://dx.doi.org/10.1161/ATVBAHA.110.213785

DOI: 10.1161/ATVBAHA.110.213785

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