Novel association of ABO histo-blood group antigen with soluble ICAM-1: results of a genome-wide association study of 6,578 women.
While circulating levels of soluble Intercellular Adhesion Molecule 1 (sICAM-1) have been associated with diverse conditions including myocardial infarction, stroke, malaria, and diabetes, comprehensive analysis of the common genetic determinants of sICAM-1 is not available. In a genome-wide association study conducted among 6,578 participants in the Women's Genome Health Study, we find that three SNPs at the ICAM1 (19p13.2) locus (rs1799969, rs5498 and rs281437) are non-redundantly associated with plasma sICAM-1 concentrations at a genome-wide significance level (P<5x10(-8)), thus extending prior results from linkage and candidate gene studies. We also find that a single SNP (rs507666, P = 5.1x10(-29)) at the ABO (9q34.2) locus is highly correlated with sICAM-1 concentrations. The novel association at the ABO locus provides evidence for a previously unknown regulatory role of histo-blood group antigens in inflammatory adhesion processes.
Paré
Guillaume
G
Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America. gpare@rics.bwh.harvard.edu
Chasman
Daniel I
DI
Kellogg
Mark
M
Zee
Robert Y L
RY
Rifai
Nader
N
Badola
Sunita
S
Miletich
Joseph P
JP
Ridker
Paul M
PM
D000017:ABO Blood-Group System / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D005260:Female; D008040:Genetic Linkage; D014644:Genetic Variation; D015894:Genome, Human; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood* / Q000235:genetics*; D009203:Myocardial Infarction / Q000276:immunology / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D012995:Solubility; D016387:Women's Health
D000017:ABO Blood-Group System; D018799:Intercellular Adhesion Molecule-1