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

TitleLarge-scale genomic studies reveal central role of ABO in sP-selectin and sICAM-1 levels.
Publication TypeJournal Article
Year of Publication2010
AuthorsBarbalic, M, Dupuis, J, Dehghan, A, Bis, JC, Hoogeveen, RC, Schnabel, RB, Nambi, V, Bretler, M, Smith, NL, Peters, A, Lu, C, Tracy, RP, Aleksic, N, Heeriga, J, Keaney, JF, Rice, K, Lip, GYH, Vasan, RS, Glazer, NL, Larson, MG, Uitterlinden, AG, Yamamoto, J, Durda, P, Haritunians, T, Psaty, BM, Boerwinkle, E, Hofman, A, Koenig, W, Jenny, NS, Witteman, JC, Ballantyne, C, Benjamin, EJ
JournalHum Mol Genet
Volume19
Issue9
Pagination1863-72
Date Published2010 May 01
ISSN1460-2083
KeywordsABO Blood-Group System, Blood Platelets, Enzyme-Linked Immunosorbent Assay, European Continental Ancestry Group, Fluorescence, Genome-Wide Association Study, Humans, Intercellular Adhesion Molecule-1, P-Selectin
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.

DOI10.1093/hmg/ddq061
Alternate JournalHum. Mol. Genet.
PubMed ID20167578
PubMed Central IDPMC2850624
Grant ListM01-RR00425 / RR / NCRR NIH HHS / United States
UL1RR025005 / RR / NCRR NIH HHS / United States
N02-HL-6-4278 / HL / NHLBI NIH HHS / United States
N01-HC-25195 / HC / NHLBI NIH HHS / United States
R01HL59367 / HL / NHLBI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
N01-HC-55015, / HC / NHLBI NIH HHS / United States
N01-HC-55022 / HC / NHLBI NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
N01-HC-55021 / HC / NHLBI NIH HHS / United States
N01-HC-85086 / HC / NHLBI NIH HHS / United States
AG028321 / AG / NIA NIH HHS / United States
U01HG004402 / HG / NHGRI NIH HHS / United States
N01-HC-35129 / HC / NHLBI NIH HHS / United States
N01 HC-55222 / HC / NHLBI NIH HHS / United States
N01-HC-55019 / HC / NHLBI NIH HHS / United States
R01HL087641 / HL / NHLBI NIH HHS / United States
N01-HC-75150 / HC / NHLBI NIH HHS / United States
N01-HC-55020 / HC / NHLBI NIH HHS / United States
N01 HC-15103 / HC / NHLBI NIH HHS / United States
HL064753 / HL / NHLBI NIH HHS / United States
HL076784 / HL / NHLBI NIH HHS / United States
DK063491 / DK / NIDDK NIH HHS / United States
N01-HC-45133 / HC / NHLBI NIH HHS / United States
N01-HC-85079 / HC / NHLBI NIH HHS / United States
R01 HL087652 / HL / NHLBI NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States
R01HL086694 / HL / NHLBI NIH HHS / United States