Coronary artery disease-related genetic variant on chromosome 10q11 is associated with carotid intima-media thickness and atherosclerosis

Stefan Kiechl, Ross C. Laxton, Qingzhong Xiao, Jussi A. Hernesniemi, Olli T. Raitakari, Mika Kähönen, Bongani M. Mayosi, Antti Jula, Leena Moilanen, Johann Willeit, Hugh Watkins, Nilesh J. Samani, Terho J. Lehtimäki, Bernard Keavney, Qingbo Xu, Shu Ye

    Research output: Contribution to journalArticlepeer-review

    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-1α (SDF-1α) 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-1α. 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 μm [95% CI, 9 to 37 μm], P=0.0014 under a fixed-effects model; and 23 μm [95% CI, 6 to 41 μm], P=0.009 under a random-effects model). In the Bruneck cohort, in which data for carotid atherosclerosis and plasma SDF-1α 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-1α 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. © 2010 American Heart Association. All rights reserved.
    Original languageEnglish
    Pages (from-to)2678-2683
    Number of pages5
    JournalArteriosclerosis, Thrombosis, and Vascular Biology
    Volume30
    Issue number12
    DOIs
    Publication statusPublished - Dec 2010

    Keywords

    • carotid atherosclerosis
    • carotid intima-media thickness
    • chromosome 10q11
    • coronary artery disease
    • stromal cell- derived factor-1α

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