Genome-wide association study to identify SNPs conferring risk of myocardial infarction and their functional analyses |
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Authors: | K. Ozaki T. Tanaka |
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Affiliation: | (1) Laboratory for Cardiovascular Diseases, SNP Research Center, the Institute of Physical and Chemical Research (RIKEN) 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan |
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Abstract: | 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-α 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.Received 7 March 2005; received after revision 22 April 2005; accepted 25 April 2005 |
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Keywords: | Myocardial infarction common disease single-nucleotide polymorphism (SNP) whole-genome association study lymphotoxin-α (LTA) galectin-2 |
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