Genome-wide association study to identify SNPs conferring risk of myocardial infarction and their functional analyses.
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.
Laboratory for Cardiovascular Diseases, SNP Research Center, the Institute of Physical and Chemical Research (RIKEN) 4-6-1, Shirokanedai, Minato-ku, Tokyo, Japan.
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Ozaki
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Tanaka
D016022:Case-Control Studies; D002462:Cell Membrane / Q000378:metabolism; D002896:Chromosomes, Human, Pair 6; D037501:Galectin 2 / Q000235:genetics* / Q000378:metabolism; D015894:Genome, Human; D006801:Humans; D015810:Linkage Disequilibrium; D008233:Lymphotoxin-alpha / Q000235:genetics* / Q000378:metabolism; D009203:Myocardial Infarction / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D021381:Protein Transport; D012306:Risk
D037501:Galectin 2; D008233:Lymphotoxin-alpha