title: Large-scale genomic studies reveal central role of ABO in sP-selectin and sICAM-1 levels.
abstract: 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.
authors.affiliation: Human Genetics Center, University of Texas Health Science Center at Houston, Houston, TX, USA. maja.barbalic@uth.tmc.edu
authors.forename: Maja
authors.initials: M
authors.lastname: Barbalic
authors.forename: Josée
authors.initials: J
authors.lastname: Dupuis
authors.forename: Abbas
authors.initials: A
authors.lastname: Dehghan
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Bis
authors.forename: Ron C
authors.initials: RC
authors.lastname: Hoogeveen
authors.forename: Renate B
authors.initials: RB
authors.lastname: Schnabel
authors.forename: Vijay
authors.initials: V
authors.lastname: Nambi
authors.forename: Monique
authors.initials: M
authors.lastname: Bretler
authors.forename: Nicholas L
authors.initials: NL
authors.lastname: Smith
authors.forename: Annette
authors.initials: A
authors.lastname: Peters
authors.forename: Chen
authors.initials: C
authors.lastname: Lu
authors.forename: Russell P
authors.initials: RP
authors.lastname: Tracy
authors.forename: Nena
authors.initials: N
authors.lastname: Aleksic
authors.forename: Jan
authors.initials: J
authors.lastname: Heeriga
authors.forename: John F
authors.initials: JF
authors.lastname: Keaney
authors.forename: Kenneth
authors.initials: K
authors.lastname: Rice
authors.forename: Gregory Y H
authors.initials: GY
authors.lastname: Lip
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Glazer
authors.forename: Martin G
authors.initials: MG
authors.lastname: Larson
authors.forename: Andre G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: Jennifer
authors.initials: J
authors.lastname: Yamamoto
authors.forename: Peter
authors.initials: P
authors.lastname: Durda
authors.forename: Talin
authors.initials: T
authors.lastname: Haritunians
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Psaty
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Koenig
authors.forename: Nancy S
authors.initials: NS
authors.lastname: Jenny
authors.forename: Jacqueline C
authors.initials: JC
authors.lastname: Witteman
authors.forename: Christie
authors.initials: C
authors.lastname: Ballantyne
authors.forename: Emelia J
authors.initials: EJ
authors.lastname: Benjamin
mesh_terms: D000017:ABO Blood-Group System / Q000235:genetics*; D001792:Blood Platelets / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005453:Fluorescence; D055106:Genome-Wide Association Study; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D019007:P-Selectin / Q000097:blood* / Q000378:metabolism; D044465:White People / Q000235:genetics*
chemical_list: D000017:ABO Blood-Group System; D019007:P-Selectin; D018799:Intercellular Adhesion Molecule-1