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.


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.
Kiechl
Stefan
S
Department of Neurology, Medical University Innsbruck, Innsbruck, Austria.
Laxton
Ross C
RC
Xiao
Qingzhong
Q
Hernesniemi
Jussi A
JA
Raitakari
Olli T
OT
Kähönen
Mika
M
Mayosi
Bongani M
BM
Jula
Antti
A
Moilanen
Leena
L
Willeit
Johann
J
Watkins
Hugh
H
Samani
Nilesh J
NJ
Lehtimäki
Terho J
TJ
Keavney
Bernard
B
Xu
Qingbo
Q
Ye
Shu
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001317:Austria; D015415:Biomarkers / Q000097:blood; D002340:Carotid Artery Diseases / Q000097:blood / Q000000981:diagnostic imaging / Q000235:genetics*; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging*; D054377:Chemokine CXCL12 / Q000097:blood / Q000235:genetics; D002879:Chromosomes, Human, Pair 10; D003324:Coronary Artery Disease / Q000235:genetics*; D042783:Endothelial Cells / Q000473:pathology; D004739:England; D005260:Female; D005387:Finland; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis; D018570:Risk Assessment; D012307:Risk Factors; D013234:Stem Cells / Q000473:pathology; D017539:Tunica Intima / Q000000981:diagnostic imaging*; D017540:Tunica Media / Q000000981:diagnostic imaging*; D014463:Ultrasonography; D055815:Young Adult
D015415:Biomarkers; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12