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-1α (SDF-1α) plasma levels. METHODS AND RESULTS: Variation on chromosome 10q11.21 has been consistently associ...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2010
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| _version_ | 1797063371782094848 |
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| author | Kiechl, S Laxton, R Xiao, Q Hernesniemi, J Raitakari, O Kähönen, M Mayosi, B Jula, A Moilanen, L Willeit, J Watkins, H Samani, N Lehtimäki, T Keavney, B Xu, Q Ye, S |
| author_facet | Kiechl, S Laxton, R Xiao, Q Hernesniemi, J Raitakari, O Kähönen, M Mayosi, B Jula, A Moilanen, L Willeit, J Watkins, H Samani, N Lehtimäki, T Keavney, B Xu, Q Ye, S |
| author_sort | Kiechl, S |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T20:58:53Z |
| format | Journal article |
| id | oxford-uuid:3a336763-4d74-4aa7-b26c-9a6ad4fb0f31 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:58:53Z |
| publishDate | 2010 |
| record_format | dspace |
| spelling | oxford-uuid:3a336763-4d74-4aa7-b26c-9a6ad4fb0f312022-03-26T14:00:07ZCoronary artery disease-related genetic variant on chromosome 10q11 is associated with carotid intima-media thickness and atherosclerosis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:3a336763-4d74-4aa7-b26c-9a6ad4fb0f31EnglishSymplectic Elements at Oxford2010Kiechl, SLaxton, RXiao, QHernesniemi, JRaitakari, OKähönen, MMayosi, BJula, AMoilanen, LWilleit, JWatkins, HSamani, NLehtimäki, TKeavney, BXu, QYe, SOBJECTIVE: 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. |
| spellingShingle | Kiechl, S Laxton, R Xiao, Q Hernesniemi, J Raitakari, O Kähönen, M Mayosi, B Jula, A Moilanen, L Willeit, J Watkins, H Samani, N Lehtimäki, T Keavney, B Xu, Q Ye, S Coronary artery disease-related genetic variant on chromosome 10q11 is associated with carotid intima-media thickness and atherosclerosis. |
| title | Coronary artery disease-related genetic variant on chromosome 10q11 is associated with carotid intima-media thickness and atherosclerosis. |
| title_full | Coronary artery disease-related genetic variant on chromosome 10q11 is associated with carotid intima-media thickness and atherosclerosis. |
| title_fullStr | Coronary artery disease-related genetic variant on chromosome 10q11 is associated with carotid intima-media thickness and atherosclerosis. |
| title_full_unstemmed | Coronary artery disease-related genetic variant on chromosome 10q11 is associated with carotid intima-media thickness and atherosclerosis. |
| title_short | Coronary artery disease-related genetic variant on chromosome 10q11 is associated with carotid intima-media thickness and atherosclerosis. |
| title_sort | coronary artery disease related genetic variant on chromosome 10q11 is associated with carotid intima media thickness and atherosclerosis |
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