title: Coronary artery disease-associated locus on chromosome 9p21 and early markers of atherosclerosis.
abstract: 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.
authors.affiliation: Department of Cardiovascular Sciences, University of Leicester, UK. njs@le.ac.uk
authors.forename: Nilesh J
authors.initials: NJ
authors.lastname: Samani
authors.forename: Olli T
authors.initials: OT
authors.lastname: Raitakari
authors.forename: Kalle
authors.initials: K
authors.lastname: Sipilä
authors.forename: Martin D
authors.initials: MD
authors.lastname: Tobin
authors.forename: Heribert
authors.initials: H
authors.lastname: Schunkert
authors.forename: Markus
authors.initials: M
authors.lastname: Juonala
authors.forename: Peter S
authors.initials: PS
authors.lastname: Braund
authors.forename: Jeanette
authors.initials: J
authors.lastname: Erdmann
authors.forename: Jorma
authors.initials: J
authors.lastname: Viikari
authors.forename: Leena
authors.initials: L
authors.lastname: Moilanen
authors.forename: Leena
authors.initials: L
authors.lastname: Taittonen
authors.forename: Antti
authors.initials: A
authors.lastname: Jula
authors.forename: Eero
authors.initials: E
authors.lastname: Jokinen
authors.forename: Tomi
authors.initials: T
authors.lastname: Laitinen
authors.forename: Nina
authors.initials: N
authors.lastname: Hutri-Kähönen
authors.forename: Markku S
authors.initials: MS
authors.lastname: Nieminen
authors.forename: Y Antero
authors.initials: YA
authors.lastname: Kesäniemi
authors.forename: Alistair S
authors.initials: AS
authors.lastname: Hall
authors.forename: Janne
authors.initials: J
authors.lastname: Hulkkonen
authors.forename: Mika
authors.initials: M
authors.lastname: Kähönen
authors.forename: Terho
authors.initials: T
authors.lastname: Lehtimäki
mesh_terms: 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