Association between the chromosome 9p21 locus and angiographic coronary artery disease burden: a collaborative meta-analysis.
OBJECTIVE
This study 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.


BACKGROUND
Chromosome 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.


METHODS
We established 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.


RESULTS
We first 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.


CONCLUSIONS
The 9p21 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.
William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University London, London, United Kingdom.
Kenneth
K
Chan
Riyaz S
RS
Patel
Paul
P
Newcombe
Christopher P
CP
Nelson
Atif
A
Qasim
Stephen E
SE
Epstein
Susan
S
Burnett
Viola L
VL
Vaccarino
A Maziar
AM
Zafari
Svati H
SH
Shah
Jeffrey L
JL
Anderson
John F
JF
Carlquist
Jaana
J
Hartiala
Hooman
H
Allayee
Kunihiko
K
Hinohara
Bok-Soo
BS
Lee
Anna
A
Erl
Katrina L
KL
Ellis
Anuj
A
Goel
Arne S
AS
Schaefer
Nour Eddine
NE
El Mokhtari
Benjamin A
BA
Goldstein
Mark A
MA
Hlatky
Alan S
AS
Go
Gong-Qing
GQ
Shen
Yan
Y
Gong
Carl
C
Pepine
Ross C
RC
Laxton
John C
JC
Whittaker
W H Wilson
WH
Tang
Julie A
JA
Johnson
Qing K
QK
Wang
Themistocles L
TL
Assimes
Ute
U
Nöthlings
Martin
M
Farrall
Hugh
H
Watkins
A Mark
AM
Richards
Vicky A
VA
Cameron
Axel
A
Muendlein
Heinz
H
Drexel
Werner
W
Koch
Jeong Euy
JE
Park
Akinori
A
Kimura
Wei-feng
WF
Shen
Iain A
IA
Simpson
Stanley L
SL
Hazen
Benjamin D
BD
Horne
Elizabeth R
ER
Hauser
Arshed A
AA
Quyyumi
Muredach P
MP
Reilly
Nilesh J
NJ
Samani
Shu
S
Ye
D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000235:genetics*; D056426:Genetic Loci; D006801:Humans; D009203:Myocardial Infarction / Q000235:genetics; D020641:Polymorphism, Single Nucleotide