|
|
Previous Article | Table of Contents | Next Article 
Blood, Vol. 92 No. 7 (October 1), 1998:
pp. 2382-2388
Nucleotide Polymorphisms in the 2 Gene Define Multiple
Alleles That Are Associated With Differences in Platelet
2 1 Density
Marcie Kritzik,
Brian Savage,
Diane J. Nugent,
Sentot Santoso,
Zaverio M. Ruggeri, and
Thomas J. Kunicki
From the Roon Research Center for Arteriosclerosis and Thrombosis,
Division of Experimental Hemostasis and Thrombosis of the Department of
Molecular and Experimental Medicine and The Department of Vascular
Biology, The Scripps Research Institute, La Jolla; the Children's
Hospital of Orange County, Orange, CA; and the Institute for Clinical
Immunology and Transfusion Medicine, Justus Liebig University, Giessen,
Germany.
Three allelic differences in the 2 gene
are associated with expression levels of the
2 1 integrin on the platelet surface. We
have previously defined two linked silent polymorphisms in the
2 gene coding region at nucleotides 807 (C or T) and 873 (G or A). We have now identified one rarer nucleotide polymorphism in
the coding region at nucleotide 837 (T or C) and four additional linked
polymorphisms within the introns that flank these coding sequences.
Moreover, we have determined that the alloantigenic Br polymorphism,
which resides in a distal coding region at nucleotide 1648, is also
linked to the 837 polymorphism. Thus, three 2 gene alleles, defined by eight nucleotide polymorphisms, have now been discovered. Allele 1 (807T/837T/873A/Brb) is associated
with increased levels of 2 1; allele 2 (807C/837T/873G/Brb) and allele 3 (807C/837C/873G/Bra) are each associated with lower levels
of 2 1. Finally, we also show here that
the rate of platelet attachment to type I collagen in whole blood under
conditions of high shear rate (1,500/s) is proportional to the density
of 2 1 receptors on the platelet surface.
Thus, the density of platelet 2 1 could
have an important impact on platelet adhesion to collagen in whole
blood and therefore on platelet function in vivo, contributing to an
increased risk of thrombosis or to bleeding in relevant disease states.

CiteULike Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
J. E. Herrera-Galeano, D. M. Becker, A. F. Wilson, L. R. Yanek, P. Bray, D. Vaidya, N. Faraday, and L. C. Becker
A Novel Variant in the Platelet Endothelial Aggregation Receptor-1 Gene Is Associated With Increased Platelet Aggregability
Arterioscler. Thromb. Vasc. Biol.,
August 1, 2008;
28(8):
1484 - 1490.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Z. M. Ruggeri and G. L. Mendolicchio
Adhesion Mechanisms in Platelet Function
Circ. Res.,
June 22, 2007;
100(12):
1673 - 1685.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. Lim, S. Carballo, J. Cornelissen, Z. A. Ali, R. Grignani, S. Bellm, and S. Large
Dose-Related Efficacy of Aspirin After Coronary Surgery in Patients With PlA2 Polymorphism (NCT00262275)
Ann. Thorac. Surg.,
January 1, 2007;
83(1):
134 - 138.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. Okumus, E. Kiyan, O. Arseven, L. Tabak, E. K. Bayrak, N. E. Unaltuna, and H. Issever
Platelet Glycoprotein Ia 807c/T and 873g/A Polymorphisms in Patients With Venous Thromboembolism
Clinical and Applied Thrombosis/Hemostasis,
January 1, 2007;
13(1):
101 - 103.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Cheli and T. J. Kunicki
hnRNP L regulates differences in expression of mouse integrin {alpha}2beta1
Blood,
June 1, 2006;
107(11):
4391 - 4398.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. V. Vijayan and P. F. Bray
Molecular Mechanisms of Prothrombotic Risk Due to Genetic Variations in Platelet Genes: Enhanced Outside-In Signaling Through the Pro33 Variant of Integrin {beta}3.
Experimental Biology and Medicine,
May 1, 2006;
231(5):
505 - 513.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Ogino, J. Kido, M. Bando, N. Hayashi, C. Wada, T. Nagata, F. Nishimura, Y. Soga, S. Takashiba, T. Kubota, et al.
{alpha}2 Integrin +807 Polymorphism in Drug-induced Gingival Overgrowth
J. Dent. Res.,
December 1, 2005;
84(12):
1183 - 1186.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. Ajzenberg, C. Berroeta, I. Philip, B. Grandchamp, P. Ducellier, V. Huart, P. Verpillat, M.-C. Guillin, and J. Benessiano
Association of the -92C/G and 807C/T Polymorphisms of the {alpha}2 Subunit Gene With Human Platelets {alpha}2{beta}1 Receptor Density
Arterioscler. Thromb. Vasc. Biol.,
August 1, 2005;
25(8):
1756 - 1760.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Mikkelsson, M. Perola, and P. J. Karhunen
Genetics of Platelet Glycoprotein Receptors: Risk of Thrombotic Events and Pharmacogenetic Implications
Clinical and Applied Thrombosis/Hemostasis,
April 1, 2005;
11(2):
113 - 125.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Cattaneo
Aspirin and Clopidogrel: Efficacy, Safety, and the Issue of Drug Resistance
Arterioscler. Thromb. Vasc. Biol.,
November 1, 2004;
24(11):
1980 - 1987.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. J. Kunicki, A. B. Federici, D. R. Salomon, J. A. Koziol, S. R. Head, T. S. Mondala, J. D. Chismar, L. Baronciani, M. T. Canciani, and I. R. Peake
An association of candidate gene haplotypes and bleeding severity in von Willebrand disease (VWD) type 1 pedigrees
Blood,
October 15, 2004;
104(8):
2359 - 2367.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. J. Kunicki
Of men; why not mice?
Blood,
May 1, 2004;
103(9):
3251 - 3252.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T.-T. Li, S. Larrucea, S. Souza, S. M. Leal, J. A. Lopez, E. M. Rubin, B. Nieswandt, and P. F. Bray
Genetic variation responsible for mouse strain differences in integrin {alpha}2 expression is associated with altered platelet responses to collagen
Blood,
May 1, 2004;
103(9):
3396 - 3402.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Lepantalo, K. S Virtanen, J. Heikkila, U. Wartiovaara, and R. Lassila
Limited early antiplatelet effect of 300 mg clopidogrel in patients with aspirin therapy undergoing percutaneous coronary interventions
Eur. Heart J.,
March 2, 2004;
25(6):
476 - 483.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Gruner, M. Prostredna, V. Schulte, T. Krieg, B. Eckes, C. Brakebusch, and B. Nieswandt
Multiple integrin-ligand interactions synergize in shear-resistant platelet adhesion at sites of arterial injury in vivo
Blood,
December 1, 2003;
102(12):
4021 - 4027.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. He, L. K. Pappan, D. G. Grenache, Z. Li, D. M. Tollefsen, S. A. Santoro, and M. M. Zutter
The contributions of the {alpha}2{beta}1 integrin to vascular thrombosis in vivo
Blood,
November 15, 2003;
102(10):
3652 - 3657.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. G. Grenache, T. Coleman, C. F. Semenkovich, S. A. Santoro, and M. M. Zutter
{alpha}2{beta}1 Integrin and Development of Atherosclerosis in a Mouse Model: Assessment of Risk
Arterioscler. Thromb. Vasc. Biol.,
November 1, 2003;
23(11):
2104 - 2109.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Best, Y. A. Senis, G. E. Jarvis, H. J. Eagleton, D. J. Roberts, T. Saito, S. M. Jung, M. Moroi, P. Harrison, F. R. Green, et al.
GPVI levels in platelets: relationship to platelet function at high shear
Blood,
October 15, 2003;
102(8):
2811 - 2818.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Dupont, P. Fontana, C. Bachelot-Loza, J.-L. Reny, I. Bieche, F. Desvard, M. Aiach, and P. Gaussem
An intronic polymorphism in the PAR-1 gene is associated with platelet receptor density and the response to SFLLRN
Blood,
March 1, 2003;
101(5):
1833 - 1840.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Chen, T. G. Diacovo, D. G. Grenache, S. A. Santoro, and M. M. Zutter
The {alpha}2 Integrin Subunit-Deficient Mouse : A Multifaceted Phenotype Including Defects of Branching Morphogenesis and Hemostasis
Am. J. Pathol.,
July 1, 2002;
161(1):
337 - 344.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. Maeno, H. Koyama, H. Tahara, M. Komatsu, M. Emoto, T. Shoji, M. Inaba, T. Miki, Y. Okuno, and Y. Nishizawa
The 807T Allele in {alpha}2 Integrin Is Protective Against Atherosclerotic Arterial Wall Thickening and the Occurrence of Plaque in Patients With Type 2 Diabetes
Diabetes,
May 1, 2002;
51(5):
1523 - 1528.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. Benze, J. Heinrich, H. Schulte, S. Rust, U. Nowak-Gottl, M.-C. Tataru, E. Kohler, G. Assmann, and R. Junker
Association of the GPIa C807T and GPIIIa PlA1/A2 polymorphisms with premature myocardial infarction in men
Eur. Heart J.,
February 2, 2002;
23(4):
325 - 330.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. J. Kunicki
The Influence of Platelet Collagen Receptor Polymorphisms in Hemostasis and Thrombotic Disease
Arterioscler. Thromb. Vasc. Biol.,
January 1, 2002;
22(1):
14 - 20.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Cadroy, K. S. Sakariassen, J.-P. Charlet, C. Thalamas, B. Boneu, and P. Sie
Role of 4 platelet membrane glycoprotein polymorphisms on experimental arterial thrombus formation in men
Blood,
November 15, 2001;
98(10):
3159 - 3161.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
W. R. P. Agema, J. W. Jukema, S. N. Pimstone, and J. J. P. Kastelein
Genetic aspects of restenosis after percutaneous coronary interventions;towards more tailored therapy
Eur. Heart J.,
November 2, 2001;
22(22):
2058 - 2074.
[PDF]
|
 |
|

|
 |

|
 |
 
K. Furihata, K. J. Clemetson, H. Deguchi, and T. J. Kunicki
Variation in Human Platelet Glycoprotein VI Content Modulates Glycoprotein VI-Specific Prothrombinase Activity
Arterioscler. Thromb. Vasc. Biol.,
November 1, 2001;
21(11):
1857 - 1863.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. S. Williams and P. F. Bray
Genetics of Arterial Prothrombotic Risk States
Experimental Biology and Medicine,
May 1, 2001;
226(5):
409 - 419.
[Abstract]
[Full Text]
|
 |
|

|
 |

|
 |
 
B. Jacquelin, M. D. Tarantino, M. Kritzik, D. Rozenshteyn, J. A. Koziol, A. T. Nurden, and T. J. Kunicki
Allele-dependent transcriptional regulation of the human integrin {alpha}2 gene
Blood,
March 15, 2001;
97(6):
1721 - 1726.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Roest, J. D. Banga, D. E. Grobbee, P. G. de Groot, J. J. Sixma, M. J. Tempelman, and Y. T. van der Schouw
Homozygosity for 807 T Polymorphism in {alpha}2 Subunit of Platelet {alpha}2{beta}1 Is Associated With Increased Risk of Cardiovascular Mortality in High-Risk Women
Circulation,
October 3, 2000;
102(14):
1645 - 1650.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Meisel, I. Cascorbi, A. Herrmann, I. Roots, M. Laule, V. Stangl, and K. Stangl
The platelet glycoprotein Ia C807T polymorphism as risk factor for coronary catheter interventions.
Blood,
September 1, 2000;
96(5):
2002 - 2003.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Roest, J. J. Sixma, Y.-P. Wu, M. J. W. Ijsseldijk, M. Tempelman, P. J. Slootweg, P. G. de Groot, and G. H. van Zanten
Platelet adhesion to collagen in healthy volunteers is influenced by variation of both alpha 2beta 1 density and von Willebrand factor
Blood,
August 15, 2000;
96(4):
1433 - 1437.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. von Beckerath, W. Koch, J. Mehilli, C. Bottiger, A. Schomig, and A. Kastrati
Glycoprotein Ia gene C807T polymorphism and risk for major adverse cardiac events within the first 30 days after coronary artery stenting
Blood,
June 1, 2000;
95(11):
3297 - 3301.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. M. Jung and M. Moroi
Signal-transducing Mechanisms Involved in Activation of the Platelet Collagen Receptor Integrin alpha 2beta 1
J. Biol. Chem.,
March 10, 2000;
275(11):
8016 - 8026.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Matsubara, M. Murata, T. Maruyama, M. Handa, N. Yamagata, G. Watanabe, T. Saruta, and Y. Ikeda
Association between diabetic retinopathy and genetic variations in alpha 2beta 1 integrin, a platelet receptor for collagen
Blood,
March 1, 2000;
95(5):
1560 - 1564.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. B. Bussel, T. J. Kunicki, and A. D. Michelson
Platelets: New Understanding of Platelet Glycoproteins and Their Role in Disease
Hematology,
January 1, 2000;
2000(1):
222 - 240.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Santoso, J. Amrhein, H. A. Hofmann, U. J.H. Sachs, M. M. Walka, H. Kroll, and V. Kiefel
A Point Mutation Thr799Met on the alpha 2 Integrin Leads to the Formation of New Human Platelet Alloantigen Sita and Affects Collagen-Induced Aggregation
Blood,
December 15, 1999;
94(12):
4103 - 4111.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. A. Santoro
Platelet Surface Collagen Receptor Polymorphisms: Variable Receptor Expression and Thrombotic/Hemorrhagic Risk
Blood,
June 1, 1999;
93(11):
3575 - 3577.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Di Paola, A. B. Federici, P.M. Mannucci, M. T. Canciani, M. Kritzik, T. J. Kunicki, and D. Nugent
Low Platelet alpha 2beta 1 Levels in Type I von Willebrand Disease Correlate With Impaired Platelet Function in a High Shear Stress System
Blood,
June 1, 1999;
93(11):
3578 - 3582.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. E. Carlsson, S. Santoso, C. Spitzer, C. Kessler, and A. Greinacher
The alpha 2 Gene Coding Sequence T807/A873 of the Platelet Collagen Receptor Integrin alpha 2beta 1 Might Be a Genetic Risk Factor for the Development of Stroke in Younger Patients
Blood,
June 1, 1999;
93(11):
3583 - 3586.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Santoso, T.J. Kunicki, H. Kroll, W. Haberbosch, and A. Gardemann
Association of the Platelet Glycoprotein Ia C807T Gene Polymorphism With Nonfatal Myocardial Infarction in Younger Patients
Blood,
April 15, 1999;
93(8):
2449 - 2453.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. Jacquelin, D. Rozenshteyn, S. Kanaji, J. A. Koziol, A. T. Nurden, and T. J. Kunicki
Characterization of Inherited Differences in Transcription of the Human Integrin alpha 2 Gene
J. Biol. C | |