Author/Authors :
Chan، نويسنده , , Kenneth and Patel، نويسنده , , Riyaz S. and Newcombe، نويسنده , , Paul and Nelson، نويسنده , , Christopher P. and Qasim، نويسنده , , Atif and Epstein، نويسنده , , Stephen E. and Burnett، نويسنده , , Susan and Vaccarino، نويسنده , , Viola L. and Zafari، نويسنده , , A. Maziar and Shah، نويسنده , , Svati H. and Anderson، نويسنده , , Jeffrey L. and Carlquist، نويسنده , , John F. and Hartiala، نويسنده , , Jaana and Allayee، نويسنده , , Hooman and Hinohara، نويسنده , , Kunihiko and Lee، نويسنده , , Bok-Soo and Erl، نويسنده , , Anna and Ellis، نويسنده , , Katrina L. and Goel، نويسنده , , Anuj and Schaefer، نويسنده , , Arne S. and El Mokhtari، نويسنده , , Nour Eddine and Goldstein، نويسنده , , Benjamin A. and Hlatky، نويسنده , , Mark A. and Go، نويسنده , , Alan S. and Shen، نويسنده , , Gong-Qing and Gong، نويسنده , , Yan and Pepine، نويسنده , , Carl and Laxton، نويسنده , , Ross C. and Whittaker، نويسنده , , John C. S. Tang، نويسنده , , W.H. Wilson and Johnson، نويسنده , , Julie A. and Wang، نويسنده , , Qing K. and Assimes، نويسنده , , Themistocles L. and Nِthlings، نويسنده , , Ute and Farrall، نويسنده , , Martin and Watkins، نويسنده , , Hugh and Richards، نويسنده , , A. Mark and Cameron، نويسنده , , Vicky A. and Muendlein، نويسنده , , Axel and Drexel، نويسنده , , Heinz-Josef Koch، نويسنده , , Werner and Park، نويسنده , , Jeong Euy and Kimura، نويسنده , , Akinori and Shen، نويسنده , , Wei-feng and Simpson، نويسنده , , Iain A. and Hazen، نويسنده , , Stanley L. and Horne، نويسنده , , Benjamin D. and Hauser، نويسنده , , Elizabeth R. and Quyyumi، نويسنده , , Arshed A. and Reilly، نويسنده , , Muredach P. and Samani، نويسنده , , Nilesh J. and Ye، نويسنده , , Shu، نويسنده ,
Abstract :
Objectives
tudy sought to ascertain the relationship of 9p21 locus with: 1) angiographic coronary artery disease (CAD) burden; and 2) myocardial infarction (MI) in individuals with underlying CAD.
ound
some 9p21 variants have been robustly associated with coronary heart disease, but questions remain on the mechanism of risk, specifically whether the locus contributes to coronary atheroma burden or plaque instability.
s
ablished a collaboration of 21 studies consisting of 33,673 subjects with information on both CAD (clinical or angiographic) and MI status along with 9p21 genotype. Tabular data are provided for each cohort on the presence and burden of angiographic CAD, MI cases with underlying CAD, and the diabetic status of all subjects.
s
st confirmed an association between 9p21 and CAD with angiographically defined cases and control subjects (pooled odds ratio [OR]: 1.31, 95% confidence interval [CI]: 1.20 to 1.43). Among subjects with angiographic CAD (n = 20,987), random-effects model identified an association with multivessel CAD, compared with those with single-vessel disease (OR: 1.10, 95% CI: 1.04 to 1.17)/copy of risk allele). Genotypic models showed an OR of 1.15, 95% CI: 1.04 to 1.26 for heterozygous carrier and OR: 1.23, 95% CI: 1.08 to 1.39 for homozygous carrier. Finally, there was no significant association between 9p21 and prevalent MI when both cases (n = 17,791) and control subjects (n = 15,882) had underlying CAD (OR: 0.99, 95% CI: 0.95 to 1.03)/risk allele.
sions
21 locus shows convincing association with greater burden of CAD but not with MI in the presence of underlying CAD. This adds further weight to the hypothesis that 9p21 locus primarily mediates an atherosclerotic phenotype.
