on January 23, 2009
Published online before print January 23, 2009, doi: 10.1161/CIRCGENETICS.108.813709
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Original Article |
Genetic Variants Associated with Myocardial Infarction risk Factors in over 8,000 Individuals from Five Ethnic Groups: The INTERHEART Genetics Study
1 Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada;
2 McGill University, Montreal, Quebec, Canada;
3 McGill University & Genome Quebec Innovation Centre, Quebec, Canada;
4 Institute of Human Genetics, Newcastle upon Tyne, UK;
5 McGill University, Montreal, Quebec & Ontario Inst. for Cancer Research, Toronto, Ontario, Canada
6 E-mail: anand{at}hhsc.ca
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.
Methods and Findings—8,795 individuals of European, South Asian, Arab, Iranian, and Nepalese origin from the INTERHEART case-control study were genotyped for 1,536 single nucleotide polymorphisms (SNPs) from 103 genes. 102 SNPs were nominally associated with MI but the statistical significance did not remain after adjustment for multiple testing. A subset of 941 SNPs from 70 genes were tested against MI risk factors. 164 SNPs are nominally associated with a MI risk factor and 14 remain significant after adjusting for multiple testing. Of these 14, 11 are associated with Apo B/A levels: eight SNPs from three genes are associated with ApoB, and three CETP SNPs are associated with ApoA1. Seven out of eight of the SNPs associated with ApoB levels were nominally associated with MI (P<0.05), while none of the three CETP SNPs were associated with MI (P
0.17). Of the 3 SNPs most significantly associated with MI, rs7412, which defines the ApoE 2 isoform, is associated with both a lower Apo B/A ratio (P =1.0 x 10-7) and lower MI risk (P=0.0004). Two LDLR variants, one intronic (rs6511720) and one in the 3'UTR (rs1433099) are both associated with a lower ApoB/A ratio (P<1.0 x 10-5) and a lower risk of MI (P=0.004 and P=0.003, respectively).
Conclusions—Fourteen common SNPs are associated with MI risk factors in 5 ethnic groups. Importantly, SNPs associated with ApoB levels appear to be associated with MI, while SNPs associated with ApoA1 levels do not. The ApoE 2 isoform, and 2 common LDLR variants (rs1433099, rs6511720) influence MI risk across multiple ethnic groups.
Key Words: myocardial infarction • risk factors • Ethnic • Genetic Variation
Related Articles
Circ Cardiovasc Genet 2009 2: 3-6.
Circ Cardiovasc Genet 2009 2: 16-25.
This article has been cited by other articles:
 |
|
 |
|
  R. McPherson A Gene-Centric Approach to Elucidating Cardiovascular Risk Circ Cardiovasc Genet, February 1, 2009; 2(1): 3 - 6. [Full Text] [PDF]
|
|