Genome-wide meta-analyses identifies seven loci associated with platelet aggregation in response to agonists

被引：220

作者：

Johnson, Andrew D. ^{[1
,2
]}

Yanek, Lisa R. ^{[3
]}

Chen, Ming-Huei ^{[1
,4
]}

Faraday, Nauder ^{[5
]}

Larson, Martin G. ^{[1
,6
]}

Tofler, Geoffrey ^{[7
]}

Lin, Shiow J. ^{[8
]}

Kraja, Aldi T. ^{[8
]}

Province, Michael A. ^{[8
]}

Yang, Qiong ^{[1
,9
]}

Becker, Diane M. ^{[3
]}

O'Donnell, Christopher J. ^{[1
,2
,10
]}

Becker, Lewis C. ^{[3
]}

机构：

[1] NHLBI, Framingham Heart Study, Framingham, MA USA

[2] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA

[3] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA

[4] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA

[5] Johns Hopkins Univ, Sch Med, Dept Anesthesia & Crit Care Med, Baltimore, MD USA

[6] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA

[7] Univ Sydney, Royal N Shore Hosp, Sydney, NSW 2006, Australia

[8] Washington Univ Med, Div Stat Genom, St Louis, MO USA

[9] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA

[10] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiol Div, Boston, MA USA

来源：

NATURE GENETICS | 2010年 / 42卷 / 07期

关键词：

GLYCOPROTEIN-VI; RECEPTOR; PROTEIN; GENE; EXPRESSION; MOLECULE; VARIANT; RESPONSIVENESS; POLYMORPHISMS; HEMOSTASIS;

D O I：

10.1038/ng.604

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Platelet function mediates both beneficial and harmful effects on human health, but few genes are known to contribute to variability in this process. We tested association of 2.5 million SNPs with platelet aggregation responses to three agonists (ADP, epinephrine and collagen) in two cohorts of European ancestry (N 2,753 in the Framingham Heart Study, N 1,238 in the Genetic Study of Atherosclerosis Risk). We identified associations of seven loci with platelet aggregation near or within GP6 (P = 4.6 × 10 13), PEAR1 (P = 3.4 × 10-12), ADRA2A (P = 3.3 × 10 11), PIK3CG (P = 3.1 × 10-9), JMJD1C (P = 1.6 × 10-8), MRVI1 (P = 2.0 × 10-8) and SHH (P = 4.5 × 10 8). Six of these loci replicated at P 0.05 in an additional African-American cohort (N 840 in the Genetic Study of Atherosclerosis Risk). These results provide insights into platelet aggregation pathways and may suggest new antiplatelet therapeutic targets. © 2010 Nature America, Inc. All rights reserved.

引用

页码：608 / U186

页数：8

共 49 条

[21] Human platelets as a substrate source for the in vitro amplification of the abnormal prion protein (PrPSc) associated with variant Creutzfeldt-Jakob disease [J].

Jones, Michael ;

Peden, Alexander H. ;

Yull, Helen ;

Wight, Darren ;

Bishop, Matthew T. ;

Prowse, Chris V. ;

Turner, Marc L. ;

Ironside, James W. ;

MacGregor, Ian R. ;

Head, Mark W. .

TRANSFUSION, 2009, 49 (02) :376-384

[22] The low-frequency allele of the platelet collagen signaling receptor glycoprotein VI is associated with reduced functional responses and expression [J].

Joutsi-Korhonen, L ;

Smethurst, PA ;

Rankin, A ;

Gray, E ;

IJsseldijk, M ;

Onley, CM ;

Watkins, NA ;

Williamson, LM ;

Goodall, AH ;

de Groot, PG ;

Famdale, RW ;

Ouwehand, WH .

BLOOD, 2003, 101 (11) :4372-4379

[23] Prevalence of impaired responsiveness to epinephrine in platelets among Japanese [J].

Kambayashi, JI ;

Shinoki, N ;

Nakamura, T ;

Ariyoshi, H ;

Kawasaki, T ;

Sakon, M ;

Monden, M .

THROMBOSIS RESEARCH, 1996, 81 (01) :85-90

[24] INVESTIGATION OF CORONARY HEART-DISEASE IN FAMILIES - FRAMINGHAM OFFSPRING STUDY [J].

KANNEL, WB ;

FEINLEIB, M ;

MCNAMARA, PM ;

GARRISON, RJ ;

CASTELLI, WP .

AMERICAN JOURNAL OF EPIDEMIOLOGY, 1979, 110 (03) :281-290

[25] The expression patterns of RGS transcripts in platelets [J].

Kim, Sung Dae ;

Sung, Hye Jin ;

Park, Sun Kyu ;

Kim, Tae Wan ;

Park, Seung Chun ;

Kim, Sang Keun ;

Cho, Jae Youl ;

Rhee, Man Hee .

PLATELETS, 2006, 17 (07) :493-497

[26] PKC-θ selectively controls the adhesion-stimulating molecule Rap1 [J].

Letschka, Thomas ;

Kollmann, Veronika ;

Pfeifhofer-Obermair, Christa ;

Lutz-Nicoladoni, Christina ;

Obermair, Gerald J. ;

Fresser, Friedrich ;

Leitges, Michael ;

Hermann-Kleiter, Natascha ;

Kaminski, Sandra ;

Baier, Gottfried .

BLOOD, 2008, 112 (12) :4617-4627

[27]

Littell R.C., 1996, SAS SYSTEMS MIXED MO

[28] A crucial role of glycoprotein VI for platelet recruitment to the injured arterial wall in vivo [J].

Massberg, S ;

Gawaz, M ;

Grüner, S ;

Schulte, V ;

Konrad, I ;

Zohlnhöfer, D ;

Heinzmann, U ;

Nieswandt, B .

JOURNAL OF EXPERIMENTAL MEDICINE, 2003, 197 (01) :41-49

[29] A Genome-wide Association Study Identifies Three Loci Associated with Mean Platelet Volume [J].

Meisinger, Christa ;

Prokisch, Holger ;

Gieger, Christian ;

Soranzo, Nicole ;

Mehta, Divya ;

Rosskopf, Dieter ;

Lichtner, Peter ;

Klopp, Norman ;

Stephens, Jonathan ;

Watkins, Nicholas A. ;

Deloukas, Panos ;

Greinacher, Andreas ;

Koenig, Wolfgang ;

Nauck, Matthias ;

Rimmbach, Christian ;

Voelzke, Henry ;

Peters, Annette ;

Illig, Thomas ;

Ouwehand, Willem H. ;

Meitinger, Thomas ;

Wichmann, H. -Erich ;

Doering, Angela .

AMERICAN JOURNAL OF HUMAN GENETICS, 2009, 84 (01) :66-71

[30] Alcohol consumption and platelet activation and aggregation among women and men: The Framingham Offspring Study [J].

Mukamal, KJ ;

Massaro, JM ;

Ault, KA ;

Mittleman, MA ;

Sutherland, PA ;

Lipinska, I ;

Levy, D ;

D'Agostino, RB ;

Tofler, GH .

ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH, 2005, 29 (10) :1906-1912

← 1 2 3 4 5 →