@article{264fa8bb9d8f4a5fbf462e1d45933549,
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 × 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.",
author = "Maja Barbalic and Jos{\'e}e Dupuis and Abbas Dehghan and Bis, {Joshua C.} and Hoogeveen, {Ron C.} and Schnabel, {Renate B.} and Vijay Nambi and Monique Bretler and Smith, {Nicholas L.} and Annette Peters and Chen Lu and Tracy, {Russell P.} and Nena Aleksic and Jan Heeriga and Keaney, {John F.} and Kenneth Rice and Lip, {Gregory Y.H.} and Vasan, {Ramachandran S.} and Glazer, {Nicole L.} and Larson, {Martin G.} and Uitterlinden, {Andre G.} and Jennifer Yamamoto and Peter Durda and Talin Haritunians and Psaty, {Bruce M.} and Eric Boerwinkle and Albert Hofman and Wolfgang Koenig and Jenny, {Nancy S.} and Witteman, {Jacqueline C.} and Christie Ballantyne and Benjamin, {Emelia J.}",
note = "Funding Information: ARIC: The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01HL087641, R01HL59367 and R01HL086694; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HHSN268200625226C. The authors thank the staff and participants of the ARIC study for their important contributions. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research. CHS: The research reported in this article was supported by contract numbers N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, grant number U01 HL080295 and R01 HL087652 from the National Heart, Lung, and Blood Institute, with additional contribution from the National Institute of Neurological Disorders and Stroke. Genotyping was supported by the Cedars-Sinai General Clinical Research Center grant M01-RR00425 and NIDDK grant DK063491 to the Southern California Diabetes Endocrinology Research Center. A full list of principal CHS investigators and institutions can be found at http://www. chs-nhlbi.org/pi.htm. FHS: This research was conducted in part using data and resources from the Framingham Heart Study of the National Heart Lung and Blood Institute of the National Institutes of Health and Boston University School of Medicine. The analyses reflect intellectual input and resource development from the Framingham Heart Study investigators participating in the SNP Health Association Resource (SHARe) project. This work was partially supported by the National Heart, Lung and Blood Institute{\textquoteright}s Framing-ham Heart Study (Contract No. N01-HC-25195) and its contract with Affymetrix, Inc for genotyping services (Contract No. N02-HL-6-4278). A portion of this research utilized the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. The work was also supported in part by grants from the National Institutes of Health HL076784, AG028321 and HL064753 to Dr Benjamin. RS: The Rotterdam Study is supported by the Erasmus Medical Center and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research; the Netherlands Organization for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly; The Netherlands Heart Foundation; the Ministry of Education, Culture and Science; the Ministry of Health Welfare and Sports; the European Commission; and the Municipality of Rotterdam. Support for gen-otyping was provided by the Netherlands Organization for Scientific Research (NWO) (175.010.2005.011, 911.03.012) and Research Institute for Diseases in the Elderly (RIDE). This study was further supported by the Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO) project nr. 050-060-810.",
year = "2010",
month = feb,
day = "18",
doi = "10.1093/hmg/ddq061",
language = "English (US)",
volume = "19",
pages = "1863--1872",
journal = "Human molecular genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "9",
}