Coronary artery disease-associated locus on chromosome 9p21 and early markers of atherosclerosis.
BACKGROUND
Genome-wide association studies have recently identified a locus on chromosome 9p21 that influences risk of coronary artery disease (CAD). The effect of the locus on early markers of atherosclerosis is unknown. We examined its association with carotid intima-media thickness (CIMT) and brachial flow-mediated dilatation (FMD).


RESULTS
We genotyped 2277 individuals, age 24 to 39 years, from the Cardiovascular Risk in Young Finns Study with CIMT and FMD measurements and 1295 individuals, age 46 to 76 years, from the Health 2000 Survey with CIMT for rs1333049, the chromosome 9p21 variant showing the strongest association with CAD. Both mean and maximum CIMT were significantly higher (P<0.001) in the older subjects of the Health 2000 Survey compared with the Young Finns Study. However, there was no association of the rs1333049 genotype with either mean or maximum CIMT at either age (P=0.959 and 0.977 for the 2 phenotypes in the Young Finns Study and P=0.714 and 0.725 in the Health 2000 Survey). Similarly, there was no association of the locus with variation in FMD in the Young Finns cohort (P=0.521).


CONCLUSIONS
The chromosome 9p21 locus does not influence CAD risk through a mechanism that also affects CIMT or induces early changes in FMD.
Samani
Nilesh J
NJ
Department of Cardiovascular Sciences, University of Leicester, UK. njs@le.ac.uk
Raitakari
Olli T
OT
Sipilä
Kalle
K
Tobin
Martin D
MD
Schunkert
Heribert
H
Juonala
Markus
M
Braund
Peter S
PS
Erdmann
Jeanette
J
Viikari
Jorma
J
Moilanen
Leena
L
Taittonen
Leena
L
Jula
Antti
A
Jokinen
Eero
E
Laitinen
Tomi
T
Hutri-Kähönen
Nina
N
Nieminen
Markku S
MS
Kesäniemi
Y Antero
YA
Hall
Alistair S
AS
Hulkkonen
Janne
J
Kähönen
Mika
M
Lehtimäki
Terho
T
D000328:Adult; D000368:Aged; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000503:physiopathology*; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000473:pathology*; D002340:Carotid Artery Diseases / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D002899:Chromosomes, Human, Pair 9; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000235:genetics*; D003430:Cross-Sectional Studies; D005260:Female; D005387:Finland; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012307:Risk Factors; D014463:Ultrasonography; D014664:Vasodilation