on July 3, 2008
Published online before print July 3, 2008, doi: 10.1161/ATVBAHA.108.170332
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Submitted on May 13, 2008
Accepted on June 22, 2008
Coronary Artery Disease–Associated Locus on Chromosome 9p21 and Early Markers of Atherosclerosis
Nilesh J. Samani *;
From the Department of Cardiovascular Sciences (N.J.S., P.B.) and Department of Health Sciences and Genetics (M.D.T.), University of Leicester, UK; the Departments of Clinical Physiology (O.T.R.) and Medicine (M.J., J.V.), University of Turku, Finland; the Departments of Pediatrics (N.H-K.), Clinical Physiology (K.S, J.H., M.K.), and Clinical Chemistry (T.L.), Tampere University Hospital and the Medical School at the University of Tampere, Finland; Medizinische Klinik II (H.S., J.E.), Universität zu Lübeck, Lübeck, Germany; the Department of Medicine (L.M.), Kuopio University Hospital, Finland; the Department of Paediatrics (L.T.), University of Oulu, Finland; the Department of Paediatrics (L.T.), Vaasa Central Hospital, Finland; the Department of Health and Functional Capacity (A.J.), National Public Health Institute, Helsinki and Turku, Finland; the Hospital for Children and Adolescents (E.J.), University of Helsinki, Finland; the Department of Clinical Physiology (T.L.), University of Kuopio, Finland; the Department of Medicine (M.S.N.), University of Helsinki, Finland; the Department of Medicine and Biocenter Oulu (Y.A.K.), University of Oulu, Finland; and the Leeds Institute for Genetics and Therapeutics (A.S.H.), University of Leeds, UK.
* To whom correspondence should be addressed. E-mail: njs{at}le.ac.uk.
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).
Methods and Results—We genotyped 2277 individuals aged 24 to 39 years from the Cardiovascular Risk in Young Finns Study with CIMT and FMD measurements and 1295 individuals, aged 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.
Key words: genetics • coronary artery diseases • atherosclerosis • carotid-intima media thickness • endothelial dysfunction
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