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

被引：207

作者：

Barbalic, Maja ^{[1
]}

Dupuis, Josee ^{[3
,5
]}

Dehghan, Abbas ^{[6
]}

Bis, Joshua C. ^{[8
]}

Hoogeveen, Ron C. ^{[12
,13
]}

Schnabel, Renate B. ^{[3
]}

Nambi, Vijay ^{[12
,13
]}

Bretler, Monique ^{[6
]}

Smith, Nicholas L. ^{[9
,14
]}

Peters, Annette ^{[15
]}

Lu, Chen ^{[5
]}

Tracy, Russell P. ^{[16
,17
]}

Aleksic, Nena ^{[12
,13
]}

Heeriga, Jan ^{[6
]}

Keaney, John F., Jr. ^{[3
]}

Rice, Kenneth ^{[10
]}

Lip, Gregory Y. H. ^{[18
]}

Vasan, Ramachandran S. ^{[3
]}

Glazer, Nicole L. ^{[8
]}

Larson, Martin G. ^{[3
]}

Uitterlinden, Andre G. ^{[7
]}

Yamamoto, Jennifer ^{[3
]}

Durda, Peter ^{[16
]}

Haritunians, Talin ^{[19
]}

Psaty, Bruce M. ^{[8
,9
,11
,20
]}

Boerwinkle, Eric ^{[1
,2
]}

Hofman, Albert ^{[6
]}

Koenig, Wolfgang ^{[21
]}

Jenny, Nancy S. ^{[16
]}

Witteman, Jacqueline C. ^{[6
]}

Ballantyne, Christie ^{[12
,13
]}

Benjamin, Emelia J. ^{[3
,4
,22
]}

机构：

[1] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX USA

[2] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX USA

[3] Boston Univ, NHLBI, Framingham Heart Study, Framingham, MA USA

[4] Boston Unvivers, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA

[5] Boston Unvivers, Sch Publ Hlth, Dept Biostat, Boston, MA USA

[6] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands

[7] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands

[8] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA

[9] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA

[10] Univ Washington, Dept Biostat, Seattle, WA 98195 USA

[11] Univ Washington, Hlth Serv, Seattle, WA 98195 USA

[12] Baylor Coll Med, Dept Med, Houston, TX 77030 USA

[13] Methodist DeBakey Heart & Vasc Ctr, Ctr Cardiovasc Dis Prevent, Houston, TX USA

[14] Seattle Epidemiol Res & Informat Ctr, Dept Vet Affairs, Off Res & Dev, Seattle, WA USA

[15] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Munich, Germany

[16] Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA

[17] Univ Vermont, Coll Med, Dept Biochem, Burlington, VT 05405 USA

[18] City Hosp, Univ Dept Med, Haemostasis Thrombosis & Vasc Biol Unit, Birmingham, W Midlands, England

[19] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA

[20] Grp Hlth Res Inst, Grp Hlth, Seattle, WA USA

[21] Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, Ulm, Germany

[22] Boston Univ, Sch Med, Dept Med, Sect Prevent Med & Epidemiol, Boston, MA 02118 USA

来源：

HUMAN MOLECULAR GENETICS | 2010年 / 19卷 / 09期

基金：

美国国家卫生研究院;

关键词：

INTERCELLULAR-ADHESION MOLECULE-1; SOLUBLE P-SELECTIN; CORONARY-HEART-DISEASE; VON-WILLEBRAND-FACTOR; WEIBEL-PALADE BODIES; BLOOD-GROUP; ATHEROSCLEROSIS RISK; CARDIOVASCULAR-DISEASE; ICAM-1; INFLAMMATION;

D O I：

10.1093/hmg/ddq061

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1863 / 1872

页数：10

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