Genetic variants associated with myocardial infarction risk factors in over 8000 individuals from five ethnic groups: The INTERHEART Genetics Study.
BACKGROUND
Myocardial infarction (MI) is a leading cause of death globally, but specific genetic variants that influence MI and MI risk factors have not been assessed on a global basis.


RESULTS
We included 8795 individuals of European, South Asian, Arab, Iranian, and Nepalese origin from the INTERHEART case-control study that genotyped 1536 single-nucleotide polymorphisms (SNPs) from 103 genes. One hundred and two SNPs were nominally associated with MI, but the statistical significance did not remain after adjustment for multiple testing. A subset of 940 SNPs from 69 genes were tested against MI risk factors. One hundred and sixty-three SNPs were nominally associated with a MI risk factor and 13 remained significant after adjusting for multiple testing. Of these 13, 11 were associated with apolipoprotein (Apo) B/A1 levels: 8 SNPs from 3 genes were associated with Apo B, and 3 cholesteryl ester transfer protein SNPs were associated with Apo A1. Seven of 8 of the SNPs associated with Apo B levels were nominally associated with MI (P<0.05), whereas none of the 3 cholesteryl ester transfer protein SNPs were associated with MI (P> or =0.17). Of the 3 SNPs most significantly associated with MI, rs7412, which defines the Apo E2 isoform, was associated with both a lower Apo B/A1 ratio (P=1.0x10(-7)) and lower MI risk (P=0.0004). Two low-density lipoprotein receptor variants, 1 intronic (rs6511720) and 1 in the 3' untranslated region (rs1433099) were both associated with a lower Apo B/A1 ratio (P<1.0x10(-5)) and a lower risk of MI (P=0.004 and P=0.003, respectively).


CONCLUSIONS
Thirteen common SNPs were associated with MI risk factors. Importantly, SNPs associated with Apo B levels were associated with MI, whereas SNPs associated with Apo A1 levels were not. The Apo E isoform, and 2 common low-density lipoprotein receptor variants (rs1433099 and rs6511720) influence MI risk in this multiethnic sample.
Anand
Sonia S
SS
Population Health Research Institute, Hamilton Health Sciences, Ontario, Canada. anands@mcmaster.ca
Xie
Changchun
C
Paré
Guillaume
G
Montpetit
Alexandre
A
Rangarajan
Sumathy
S
McQueen
Matthew J
MJ
Cordell
Heather J
HJ
Keavney
Bernard
B
Yusuf
Salim
S
Hudson
Thomas J
TJ
Engert
James C
JC
D000483:Alleles; D016632:Apolipoprotein A-I / Q000097:blood / Q000235:genetics; D053329:Apolipoprotein E2 / Q000097:blood / Q000235:genetics; D001055:Apolipoproteins B / Q000097:blood / Q000235:genetics; D018912:Arabs / Q000235:genetics; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D053480:Cholesterol Ester Transfer Proteins / Q000097:blood / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007492:Iran; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000208:ethnology* / Q000235:genetics*; D009390:Nepal; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011973:Receptors, LDL / Q000097:blood / Q000235:genetics; D012307:Risk Factors; D044465:White People / Q000235:genetics
D016632:Apolipoprotein A-I; D053329:Apolipoprotein E2; D001055:Apolipoproteins B; D053480:Cholesterol Ester Transfer Proteins; D011973:Receptors, LDL