Published online before print January 23, 2009, doi: 10.1161/CIRCGENETICS.108.813709
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Original Articles |
Genetic Variants Associated With Myocardial Infarction Risk Factors in Over 8000 Individuals From Five Ethnic Groups
The INTERHEART Genetics Study
From the Population Health Research Institute, Hamilton Health Sciences (S.S.A., C.X., S.R., M.J.M., S.Y.); Departments of Medicine and Clinical Epidemiology and Biostatistics (S.S.A., C.X., S.Y.), and Pathology and Molecular Medicine (M.J.M.), McMaster University, Hamilton, Ontario, Canada; McGill University and Genome Quebec Innovation Centre (G.P., A.M., T.J.H.); Departments of Medicine (T.J.H., J.C.E.) and Human Genetics (G.P., T.J.H., J.C.E.), McGill University, Montreal, Quebec, Canada; Institute of Human Genetics (H.J.C., B.K.), Newcastle upon Tyne, United Kingdom; and Ontario Institute for Cancer Research (T.J.H.), Toronto, Ontario, Canada.
Correspondence to Sonia S. Anand, MD, PhD, FRCPc, Hamilton General Hospital, 237 Barton Street E. 4 East Rm. 439, Hamilton, ON, Canada L8L 2X2. E-mail anands{at}mcmaster.ca
Received August 11, 2008; accepted December 4, 2008.
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 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
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.
Key Words: genetic variation • myocardial infarction • ethnic groups • risk factors
CLINICAL PERSPECTIVE
The online Data Supplement is available at http://circgenetics.ahajournals.org/cgi/content/full/CIRCGENETICS.108.813709/DC1.
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