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

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

    Arteriosclerosis, thrombosis, and vascular biology. 2010;30(12):2678-83.

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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-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). CONCLUSIONS: The coronary heart disease-related variant at the 10q11.21 locus is associated with carotid IMT and atherosclerosis.

    Bibliographic metadata

    Type of resource:
    Content type:
    Publication type:
    Published date:
    Abbreviated journal title:
    ISSN:
    Place of publication:
    United States
    Volume:
    30
    Issue:
    12
    Pagination:
    2678-83
    Digital Object Identifier:
    10.1161/ATVBAHA.110.213785
    Pubmed Identifier:
    20847302
    Pii Identifier:
    ATVBAHA.110.213785
    Access state:
    Active

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    Record metadata

    Manchester eScholar ID:
    uk-ac-man-scw:201233
    Created by:
    Price, Caroline
    Created:
    11th July, 2013, 14:29:23
    Last modified by:
    Price, Caroline
    Last modified:
    11th July, 2013, 14:29:23

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