TY - JOUR
T1 - Genome-Wide Association Study for Circulating Tissue Plasminogen Activator Levels and Functional Follow-Up Implicates Endothelial STXBP5 and STX2
AU - Huang, Jie
AU - Huffman, Jennifer E.
AU - Yamkauchi, Munekazu
AU - Trompet, Stella
AU - Asselbergs, Folkert W.
AU - Sabater-Lleal, Maria
AU - Tregouet, David-Alexandre
AU - Chen, Wei-Min
AU - Smith, Nicholas L.
AU - Kleber, Marcus E.
AU - Shin, So-Youn
AU - Becker, Diane M.
AU - Tang, Weihong
AU - Dehghan, Abbas
AU - Johnson, Andrew D.
AU - Vinh Truong, [No Value]
AU - Folkersen, Lasse
AU - Yang, Qiong
AU - Oudot-Mellkah, Tiphaine
AU - Buckley, Brendan M.
AU - Moore, Jason H.
AU - Williams, Frances M. K.
AU - Campbell, Harry
AU - Silbernagel, Guenther
AU - Vitart, Veronique
AU - Rudan, Igor
AU - Tofler, Geoffrey H.
AU - Navis, Gerjan J.
AU - DeStefano, Anita
AU - Wright, Alan F.
AU - Chen, Ming-Huei
AU - de Craen, Anton J. M.
AU - Worrall, Bradford B.
AU - Rudnicka, Alicja R.
AU - Rumley, Ann
AU - Bookman, Ebony B.
AU - Psaty, Bruce M.
AU - Chen, Fang
AU - Keene, Keith L.
AU - Franco, Oscar H.
AU - Boehm, Bernhard O.
AU - Uitterlinden, Andre G.
AU - Carter, Angela M.
AU - Jukema, J. Wouter
AU - Sattar, Naveed
AU - Bis, Joshua C.
AU - Ikram, Mohammad A.
AU - van Gilst, Wiek H.
AU - Hillege, Hans L.
AU - van der Harst, Pim
AU - CHARGE Consortium Hemostatic
PY - 2014/5
Y1 - 2014/5
N2 - Objective Tissue plasminogen activator (tPA), a serine protease, catalyzes the conversion of plasminogen to plasmin, the major enzyme responsible for endogenous fibrinolysis. In some populations, elevated plasma levels of tPA have been associated with myocardial infarction and other cardiovascular diseases. We conducted a meta-analysis of genome-wide association studies to identify novel correlates of circulating levels of tPA.Approach and Results Fourteen cohort studies with tPA measures (N=26 929) contributed to the meta-analysis. Three loci were significantly associated with circulating tPA levels (PConclusions We identified 3 loci associated with circulating tPA levels, the PLAT region, STXBP5, and STX2. Our functional studies implicate a novel role for STXBP5 and STX2 in regulating tPA release.
AB - Objective Tissue plasminogen activator (tPA), a serine protease, catalyzes the conversion of plasminogen to plasmin, the major enzyme responsible for endogenous fibrinolysis. In some populations, elevated plasma levels of tPA have been associated with myocardial infarction and other cardiovascular diseases. We conducted a meta-analysis of genome-wide association studies to identify novel correlates of circulating levels of tPA.Approach and Results Fourteen cohort studies with tPA measures (N=26 929) contributed to the meta-analysis. Three loci were significantly associated with circulating tPA levels (PConclusions We identified 3 loci associated with circulating tPA levels, the PLAT region, STXBP5, and STX2. Our functional studies implicate a novel role for STXBP5 and STX2 in regulating tPA release.
KW - fibrinolysis
KW - genome-wide association study
KW - hemostasis
KW - meta-analysis
KW - tissue plasminogen activator
KW - VON-WILLEBRAND-FACTOR
KW - CORONARY-ARTERY-DISEASE
KW - ACUTE ISCHEMIC-STROKE
KW - MYOCARDIAL-INFARCTION
KW - PLASMA-LEVELS
KW - GENETIC-VARIATION
KW - RISK
KW - HEART
KW - POLYMORPHISMS
KW - INHIBITOR-1
U2 - 10.1161/ATVBAHA.113.302088
DO - 10.1161/ATVBAHA.113.302088
M3 - Article
VL - 34
SP - 1093
EP - 1101
JO - Arteriosclerosis thrombosis and vascular biology
JF - Arteriosclerosis thrombosis and vascular biology
SN - 1079-5642
IS - 5
ER -