Association of the 9p21.3 locus with risk of first-ever myocardial infarction in Pakistanis: case-control study in South Asia and updated meta-analysis of Europeans.
OBJECTIVE
To examine variants at the 9p21 locus in a case-control study of acute myocardial infarction (MI) in Pakistanis and to perform an updated meta-analysis of published studies in people of European ancestry.


RESULTS
A total of 1851 patients with first-ever confirmed MI and 1903 controls were genotyped for 89 tagging single-nucleotide polymorphisms at locus 9p21, including the lead variant (rs1333049) identified by the Wellcome Trust Case Control Consortium. Minor allele frequencies and extent of linkage disequilibrium observed in Pakistanis were broadly similar to those seen in Europeans. In the Pakistani study, 6 variants were associated with MI (P<10(-2)) in the initial sample set, and in an additional 741 cases and 674 controls in whom further genotyping was performed for these variants. For Pakistanis, the odds ratio for MI was 1.13 (95% CI, 1.05 to 1.22; P=2 x 10(-3)) for each copy of the C allele at rs1333049. In comparison, a meta-analysis of studies in Europeans yielded an odds ratio of 1.31 (95% CI, 1.26 to 1.37) for the same variant (P=1 x 10(-3) for heterogeneity). Meta-analyses of 23 variants, in up to 38,250 cases and 84,820 controls generally yielded higher values in Europeans than in Pakistanis.


CONCLUSIONS
To our knowledge, this study provides the first demonstration that variants at the 9p21 locus are significantly associated with MI risk in Pakistanis. However, association signals at this locus were weaker in Pakistanis than those in European studies.
Saleheen
Danish
D
Center for Non-Communicable Diseases, Karachi, Pakistan. danish.saleheen@cncdpk.com
Alexander
Myriam
M
Rasheed
Asif
A
Wormser
David
D
Soranzo
Nicole
N
Hammond
Naomi
N
Butterworth
Adam
A
Zaidi
Moazzam
M
Haycock
Philip
P
Bumpstead
Suzannah
S
Potter
Simon
S
Blackburn
Hannah
H
Gray
Emma
E
Di Angelantonio
Emanuele
E
Kaptoge
Stephen
S
Shah
Nabi
N
Samuel
Maria
M
Janjua
Ahmedyar
A
Sheikh
Nasir
N
Haider
Shajjia Razi
SR
Murtaza
Muhammed
M
Ahmad
Usman
U
Hakeem
Abdul
A
Memon
Muhammad Ali
MA
Mallick
Nadeem Hayat
NH
Azhar
Muhammad
M
Samad
Abdus
A
Rasheed
Syed Zahed
SZ
Gardezi
Ali Raza
AR
Memon
Nazir Ahmed
NA
Ghaffar
Abdul
A
Memon
Fazal-ur-Rehman
FU
Zaman
Khan Shah
KS
Kundi
Assadullah
A
Yaqoob
Zia
Z
Cheema
Liaquat Ali
LA
Qamar
Nadeem
N
Faruqui
Azhar
A
Jooma
Rashid
R
Niazi
Jawaid Hassan
JH
Hussain
Mustafa
M
Kumar
Kishore
K
Saleem
Asim
A
Kumar
Kishwar
K
Daood
Muhammad Salman
MS
Memon
Fatima
F
Gul
Aftab Alam
AA
Abbas
Shahid
S
Zafar
Junaid
J
Shahid
Faisal
F
Memon
Zehra
Z
Bhatti
Shahzad Majeed
SM
Kayani
Waleed
W
Ali
Syed Saadat
SS
Fahim
Muhammad
M
Ishaq
Muhammad
M
Frossard
Philippe
P
Deloukas
Panos
P
Danesh
John
J
D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002899:Chromosomes, Human, Pair 9; D005060:Europe; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000208:ethnology / Q000235:genetics*; D016017:Odds Ratio; D010154:Pakistan; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D012307:Risk Factors; D044465:White People / Q000235:genetics*