Large-scale genomic studies reveal central role of ABO in sP-selectin and sICAM-1 levels
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-...
Saved in:
Published in | Human molecular genetics Vol. 19; no. 9; pp. 1863 - 1872 |
---|---|
Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford
Oxford University Press
01.05.2010
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | 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 × 10−61) and for sICAM-1 levels within the ICAM-1 gene (rs3093030, P = 3.53 × 10−23). Both sP-selectin and sICAM-1 were associated with ABO gene variants (rs579459, P = 1.86 × 10−41 and rs649129, P = 1.22 × 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. |
---|---|
Bibliography: | These authors contributed equally to this work. ArticleID:ddq061 ark:/67375/HXZ-KRHTZ65T-G istex:BA6E6CAC2AA109BA18C49129ADC13D0A6A828CF6 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1 |
ISSN: | 0964-6906 1460-2083 |
DOI: | 10.1093/hmg/ddq061 |