Functional variation in LGALS2 confers risk of myocardial infarction and regulates lymphotoxin-alpha secretion in vitro.
Myocardial infarction (MI) has become one of the leading causes of death in the world. Its pathogenesis includes chronic formation of plaque inside the vessel wall of the coronary artery and acute rupture of the artery, implicating a number of inflammation-mediating molecules, such as the cytokine lymphotoxin-alpha (LTA). Functional variations in LTA are associated with susceptibility to MI. Here we show that LTA protein binds to galectin-2, a member of the galactose-binding lectin family. Our case-control association study in a Japanese population showed that a single nucleotide polymorphism in LGALS2 encoding galectin-2 is significantly associated with susceptibility to MI. This genetic substitution affects the transcriptional level of galectin-2 in vitro, potentially leading to altered secretion of LTA, which would then affect the degree of inflammation; however, its relevance to other populations remains to be clarified. Smooth muscle cells and macrophages in the human atherosclerotic lesions expressed both galectin-2 and LTA. Our findings thus suggest a link between the LTA cascade and the pathogenesis of MI.
Ozaki
Kouichi
K
Laboratory for Cardiovascular Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Tokyo 108-8639, Japan.
Inoue
Katsumi
K
Sato
Hiroshi
H
Iida
Aritoshi
A
Ohnishi
Yozo
Y
Sekine
Akihiro
A
Sato
Hideyuki
H
Odashiro
Keita
K
Nobuyoshi
Masakiyo
M
Hori
Masatsugu
M
Nakamura
Yusuke
Y
Tanaka
Toshihiro
T
D016022:Case-Control Studies; D037501:Galectin 2 / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007249:Inflammation / Q000235:genetics; D007438:Introns / Q000235:genetics; D007564:Japan; D019169:Jurkat Cells; D008233:Lymphotoxin-alpha / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D009203:Myocardial Infarction / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism; D020798:Two-Hybrid System Techniques
D037501:Galectin 2; D008233:Lymphotoxin-alpha; D034741:RNA, Small Interfering; D014404:Tubulin