TY - JOUR
T1 - Coronary artery disease-related genetic variant on chromosome 10q11 is associated with carotid intima-media thickness and atherosclerosis
AU - Kiechl, Stefan
AU - Laxton, Ross C.
AU - Xiao, Qingzhong
AU - Hernesniemi, Jussi A.
AU - Raitakari, Olli T.
AU - Kähönen, Mika
AU - Mayosi, Bongani M.
AU - Jula, Antti
AU - Moilanen, Leena
AU - Willeit, Johann
AU - Watkins, Hugh
AU - Samani, Nilesh J.
AU - Lehtimäki, Terho J.
AU - Keavney, Bernard
AU - Xu, Qingbo
AU - Ye, Shu
N1 - , British Heart Foundation, United Kingdom
PY - 2010/12
Y1 - 2010/12
N2 - 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.
AB - 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.
KW - carotid atherosclerosis
KW - carotid intima-media thickness
KW - chromosome 10q11
KW - coronary artery disease
KW - stromal cell- derived factor-1α
U2 - 10.1161/ATVBAHA.110.213785
DO - 10.1161/ATVBAHA.110.213785
M3 - Article
C2 - 20847302
SN - 1079-5642
VL - 30
SP - 2678
EP - 2683
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
IS - 12
ER -