Genome-wide association study to identify SNPs conferring risk of myocardial infarction and their functional analyses

Cell Mol Life Sci. 2005 Aug;62(16):1804-13. doi: 10.1007/s00018-005-5098-z.


Myocardial infarction might result from the interactions of multiple genetic and environmental factors, none of which can cause disease solely by each of themselves. Although molecular biological studies revealed that a number of proteins are possibly involved in its pathogenesis, little, if any genetic findings have been reported so far. To reveal genetic backgrounds of myocardial infarction, we performed a large-scale, case-control association study using 92,788 gene-based single-nucleotide polymorphism (SNP) markers. We have identified functional SNPs within the lymphotoxin-alpha gene (LTA) located on chromosome 6p21 that conferred susceptibility to myocardial infarction. Furthermore, we could identify galectin-2 protein as a binding partner of LTA protein. The association study further revealed that a functional SNP in LGALS2 encoding galectin-2, which led to altered secretion of LTA, also indicated a risk of myocardial infarction. A combined strategy of genetic and molecularcellular biological approaches may be useful in clarifying pathogenesis of common diseases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Case-Control Studies
  • Cell Membrane / metabolism
  • Chromosomes, Human, Pair 6
  • Galectin 2 / genetics*
  • Galectin 2 / metabolism
  • Genome, Human*
  • Humans
  • Linkage Disequilibrium
  • Lymphotoxin-alpha / genetics*
  • Lymphotoxin-alpha / metabolism
  • Myocardial Infarction / genetics*
  • Myocardial Infarction / metabolism
  • Polymorphism, Single Nucleotide*
  • Protein Transport
  • Risk


  • Galectin 2
  • Lymphotoxin-alpha