Genetic variants associated with myocardial infarction risk factors in over 8000 individuals from five ethnic groups: The INTERHEART Genetics Study

Circ Cardiovasc Genet. 2009 Feb;2(1):16-25. doi: 10.1161/CIRCGENETICS.108.813709. Epub 2009 Jan 23.

Abstract

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> 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Apolipoprotein A-I / blood
  • Apolipoprotein A-I / genetics
  • Apolipoprotein E2 / blood
  • Apolipoprotein E2 / genetics
  • Apolipoproteins B / blood
  • Apolipoproteins B / genetics
  • Arabs / genetics
  • Asian People / genetics
  • Case-Control Studies
  • Cholesterol Ester Transfer Proteins / blood
  • Cholesterol Ester Transfer Proteins / genetics
  • Female
  • Genotype
  • Humans
  • Iran
  • Male
  • Middle Aged
  • Myocardial Infarction / ethnology*
  • Myocardial Infarction / genetics*
  • Nepal
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Receptors, LDL / blood
  • Receptors, LDL / genetics
  • Risk Factors
  • White People / genetics

Substances

  • Apolipoprotein A-I
  • Apolipoprotein E2
  • Apolipoproteins B
  • Cholesterol Ester Transfer Proteins
  • Receptors, LDL