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Barbalic, M.* ; Dupuis, J.* ; Dehghan, A.* ; Bis, J.C.* ; Hoogeveen, R.C.* ; Schnabel, R.B.* ; Nambi, V.* ; Bretler, M.* ; Smith, N.L.* ; Peters, A. ; Lu, C.* ; Tracy, R.P.* ; Aleksic, N.* ; Heeriga, J.* ; Keaney, J.F.* ; Rice, K.* ; Lip, G.Y.H.* ; Vasan, R.S.* ; Glazer, N.L.* ; Larson, M.G.* ; Uitterlinden, A.G.* ; Yamamoto, J.* ; Durda, P.* ; Haritunians, T.* ; Psaty, B.M.* ; Boerwinkle, E.* ; Hofman, A.* ; Koenig, W.* ; Jenny, N.S.* ; Witteman, J.C.* ; Ballantyne, C.* ; Benjamin, E.J.*

Large-scale genomic studies reveal central role of ABO in sP-selectin and sICAM-1 levels.

Hum. Mol. Genet. 19, 1863-1872 (2010)
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P-selectin and intercellular adhesion molecule-1 (ICAM-1) participate in inflammatory processes by promoting adhesion of leukocytes to vascular wall endothelium. Their soluble levels have been associated with adverse cardiovascular events. To identify loci affecting soluble levels of P-selectin (sP-selectin) and ICAM-1 (sICAM-1), we performed a genome-wide association study in a sample of 4115 (sP-selectin) and 9813 (sICAM-1) individuals of European ancestry as a part of The Cohorts for Heart and Aging Research in Genome Epidemiology consortium. The most significant SNP association for sP-selectin was within the SELP gene (rs6136, P = 4.05 x 10(-61)) and for sICAM-1 levels within the ICAM-1 gene (rs3093030, P = 3.53 x 10(-23)). Both sP-selectin and sICAM-1 were associated with ABO gene variants (rs579459, P = 1.86 x 10(-41) and rs649129, P = 1.22 x 10(-15), respectively) and in both cases the observed associations could be accounted for by the A1 allele of the ABO blood group. The absence of an association between ABO blood group and platelet-bound P-selectin levels in an independent subsample (N = 1088) from the ARIC study, suggests that the ABO blood group may influence cleavage of the P-selectin protein from the cell surface or clearance from the circulation, rather than its production and cellular presentation. These results provide new insights into adhesion molecule biology.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter INTERCELLULAR-ADHESION MOLECULE-1; HUMAN-ENDOTHELIAL-CELLS; SOLUBLE P-SELECTIN; PLASMODIUM-FALCIPARUM MALARIA; CORONARY-ARTERY-DISEASE; VON-WILLEBRAND-FACTOR; WEIBEL-PALADE BODIES; BLOOD-GROUP; CARDIOVASCULAR-DISEASE; ATHEROSCLEROSIS RISK
Sprache englisch
Veröffentlichungsjahr 2010
HGF-Berichtsjahr 2010
ISSN (print) / ISBN 0964-6906
e-ISSN 1460-2083
Zeitschrift Human Molecular Genetics
Quellenangaben Band: 19, Heft: 9, Seiten: 1863-1872 Artikelnummer: , Supplement: ,
Verlag Oxford University Press
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology (EPI)
PSP-Element(e) G-503900-005
PubMed ID 20167578
DOI 10.1093/hmg/ddq061
WOS ID WOS:000276526700020
Scopus ID 77952534219
Erfassungsdatum 2010-07-26
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