This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Carlsson, L. E. Articles by Kessler, C. Search for Related Content PubMed PubMed Citation Articles by Carlsson, L. E. Articles by Kessler, C.

(Stroke. 1997;28:1392-1395.)
© 1997 American Heart Association, Inc.

Articles

Polymorphisms of the Human Platelet Antigens HPA-1, HPA-2, HPA-3, and HPA-5 on the Platelet Receptors for Fibrinogen (GPIIb/IIIa), von Willebrand Factor (GPIb/IX), and Collagen (GPIa/IIa) Are Not Correlated With an Increased Risk for Stroke

Lena E. Carlsson, MSc; Andreas Greinacher, MD; Carsten Spitzer, MD; Reinhard Walther, PhD; Christof Kessler, MD

From the Departments of Immunology and Transfusion Medicine (L.E.C., A.G.), Neurology (C.S., C.K.), and Biochemistry (R.W.), Ernst-Moritz-Arndt-University, Greifswald, Germany.

Correspondence to A. Greinacher, Department of Immunology and Transfusion Medicine, Ernst-Moritz-Arndt-University, Sauerbruchstr, D-17487 Greifswald, Germany. E-mail greinach{at}rz.uni-greifswald.de

	Abstract

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Background and Purpose A recent study has described a high incidence of the human platelet antigen (HPA)-1b alloantigen in patients with myocardial infarction. We investigated the distribution of gene polymorphisms of platelet glycoproteins (GPs) in patients with cerebrovascular disease (CVD) and stroke. The polymorphic systems we have studied are HPA-1 and HPA-3 on the fibrinogen receptor (GPIIb/IIIa), HPA-2 on the von Willebrand factor receptor (GPIb/IX), and HPA-5 on one of the platelet collagen receptors (GPIa/IIa).

Methods DNA was isolated from peripheral blood collected from 218 consecutive stroke patients, 165 neurological inpatients without signs of CVD, and 321 healthy blood donors. The genotypes of HPA-1, HPA-2, HPA-3, and HPA-5 were determined by sequence specific primer polymerase chain reactions.

Results The calculated allele frequencies were as follows: for CVD patients, HPA-1a/b 0.81/0.19, HPA-2a/b 0.91/0.09, HPA-3a/b 0.61/0.39, and HPA-5a/b 0.92/0.08; for inpatients, HPA-1a/b 0.83/0.17, HPA-2a/b 0.91/0.09, HPA-3a/b 0.62/0.38, and HPA-5a/b 0.93/0.07; and for blood donors, HPA-1a/b 0.85/0.15, HPA-2a/b 0.94/0.06, HPA-3a/b 0.60/0.40, and HPA-5a/b 0.92/0.08. There were no statistically significant differences for the analyzed HPA polymorphism frequencies either between the CVD patients and the non-CVD inpatients or the CVD patients and blood donors. However, the HPA-1b genotype was slightly more frequent in patients (CVD and non-CVD) than in the healthy blood donors.

Conclusions Our results indicate that the HPA-1, HPA-2, HPA-3, and HPA-5 polymorphisms are not associated with an increased risk for stroke.

Key Words: antigens, human platelet • collagen • fibrinogen • platelets • polymorphism (genetics) • von Willebrand factor

	Introduction

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Platelets are crucial in primary hemostasis. Platelet-dependent thromboembolism is an underlying mechanism in the pathogenesis of stroke. Platelets adhere to subendothelial structures by specific receptors such as the collagen receptor GPIa/IIa or the primary vWF receptor GPIb/IX. After adhesion, platelets become activated and finally aggregate by cross-linking via the fibrinogen receptor GPIIb/IIIa. The receptors for vWF (GPIb/IX), fibrinogen (GPIIa/IIIb), and collagen (GPIa/IIa) are polymorphic. Until recently, the only major clinical relevance of these polymorphisms has been attributed to their capability to induce an immune response leading to the production of alloantibodies, causing immune-mediated platelet disorders.¹ However, platelet GP polymorphisms might also affect the sensitivity of these important receptors, thus influencing platelet susceptibility to activating and aggregating stimuli. Weiss et al² reported data suggesting that the HPA-1b allele might be a predisposing factor for myocardial infarction. This hypothesis is currently under discussion.^{3 4 5 6 7}

The polymorphisms of the human platelet alloantigens are caused by single base-pair substitutions resulting in an amino acid replacement. The receptor complex GPIIb/IIIa carries two major polymorphic sites, HPA-1 (bp T196C, amino acid Leu33Pro)⁸ and HPA-3 (bp T2622G, amino acid Ile843Ser).⁹ On the vWF receptor GPIb/IX, the HPA-2 polymorphism is expressed (bp T524C, amino acid Met145Thr).¹⁰ This polymorphism is not involved in the binding of vWF to GPIb/IX.¹¹ The collagen receptor GPIa/IIa carries the HPA-5 polymorphic system (bp G1648A, amino acid Glu505Lys).¹²

In vitro experiments have not resolved any major functional differences of these polymorphisms. However, this might not reflect the in vivo situation as suggested by the study of Weiss et al.² Because these polymorphisms might also be important for the development of CVD, we assessed the correlation between four HPA polymorphisms and the incidence of stroke in a large group of consecutive stroke patients compared with other neurological inpatients and healthy blood donors.

Determination of the phenotype of the polymorphic platelet receptors by means of human alloantibodies¹³ is limited by their availability. This has partially been solved for the HPA-1 system by the use of monoclonal antibodies,^{14 15 16} but at present this alternative is not available for HPA-2, HPA-3, and HPA-5. In the present study, we have overcome these problems by the determination of the HPA genotypes.

	Subjects and Methods

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Study Design and Patients
Blood samples were collected from a consecutive series of 218 CVD patients from November 1, 1995, until July 31, 1996, who were admitted to the stroke service of the Department of Neurology of the Ernst-Moritz-Arndt-University, Greifswald, Germany. We included only patients with focal neurological symptoms due to cerebral ischemia. Patients with intracerebral or subarachnoid hemorrhage or patients with a stroke due to vasculitis were excluded. The CVD patients were compared with two control groups. The first one consisted of 165 neurological inpatients showing no acute or recent signs for CVD or any other condition in which vascular pathology plays a major role, such as migraine or arteriovenous malformations. Healthy blood donors (n=321) served as a second control group. All patients gave informed consent to the study.

DNA Preparation and Genotyping
DNA was prepared from 5 mL of whole blood according to Miller et al¹⁷ or from 250 µL buffy coat with the QIAamp blood kit (Qiagen GmbH). The primers, HPA-1, HPA-2, HPA-3, and HPA-5 specific and internal control (C-reactive protein gene), were purchased from Eurogentec (Seraing). The allele-specific PCR was performed as described¹⁸ with modifications.¹⁹ The final reaction mixture contains 0.5 U AmpliTaq Gold (Perkin Elmer), 2 µL 10x reaction buffer supplied by the manufacturer, 1.5 mmol/L MgCl, 0.8 mmol/L dNTP, 0.5 µmol/L of each specific primer, and 0.15 µmol/L of each internal control primer. DNA was added to a final concentration of 100 ng/20 µL reaction. The PCR was run in a GeneAmp PCR System 2400 (Perkin Elmer) under the following conditions: 10 minutes at 95°C for enzyme activation, 10 cycles of 10 seconds at 95°C, 30 seconds at 65°C, and 30 seconds at 72°C, followed by 22 cycles with a decreased annealing temperature of 58°C. The amplification products were analyzed by agarose gel electrophoresis and ethidium bromide staining.

Statistical Analysis
The statistical analysis was performed with the Statistical Package for the Social Sciences (SPSS PC+, version 4.0) software. Genotype distribution and allele frequencies were compared by cross-tables using the ² test. Significance level was established at a value of P.05.

	Results

Top Abstract Introduction Subjects and Methods Results Discussion References

 
A total of 218 patients, 116 women (53.2%) and 102 men (46.8), suffering from CVD were included in the study. The mean±SD age was 62.1±14.3 years (range, 16 to 90 years). Thirty-eight patients (17.4%) presented with transient ischemic attack, and 180 patients (82.6%) suffered from completed stroke as shown by cranial CT or cranial MRI. CVD pathogenesis was thromboembolic in 184 patients (84.4%) and microangiopathic in 34 patients (15.6%). Of the conventional risk factors, hypertension was found in 148 patients (67.9%), diabetes in 71 patients (32.6%), high serum cholesterol in 41 patients (18.8%), and smoking (current or ex-smoker) in 73 patients (33.5%).

The mean±SD age was 59.0±14.2 years (range, 25 to 88 years) for the non-CVD neurological inpatients and 30.6±9.2 years (range, 19 to 60 years) for the healthy blood donors. In the neurological inpatient group, there were 88 female patients (53.3%); among the blood donors, there were 148 women (46.0%). There were no significant differences in the sex ratio among the three groups (²=3.74, P.15).

The comparison of genotype distribution in CVD patients and neurological inpatients or CVD patients and healthy blood donors did not reveal any significant differences in the frequencies of HPA-1, HPA-2, HPA-3, and HPA-5 genotypes (Table 1). Also, the allele frequencies of HPA-1, HPA-2, HPA-3, and HPA-5 in the different groups did not differ significantly (Table 2).

View this table: [in this window] [in a new window]   Table 1. Distribution of HPA-1, HPA-2, HPA-3, and HPA-5 Genotypes in Blood Donors, CVD Patients, and Non-CVD Inpatients

View this table: [in this window] [in a new window]   Table 2. Distribution of Allele Frequencies in Blood Donors, CVD Patients, and Non-CVD Inpatients

	Discussion

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Clinical studies have demonstrated that antiplatelet agents are effective in preventing thromboembolic complications in the arterial system, eg, in stroke patients.^{20 21} There is evidence for platelet-dependent thrombosis in CVD patients even under therapy with antiplatelet agents.²² The reason for this could be a genetically determined predisposition for hyperaggregability in a subgroup of CVD patients, which might be mediated by polymorphic receptors involved in platelet adhesion and aggregation. However, data on this topic are lacking. For this purpose, we conducted a pilot study to determine the genotype distribution of polymorphisms of the platelet receptors for fibrinogen, collagen, and vWF in CVD patients.

Our results indicate that there is no correlation between the genotypes of the platelet receptor polymorphisms HPA-1, HPA-2, HPA-3, and HPA-5 and stroke. However, the CVD-stroke patients and the inpatient control group showed an increased prevalence of HPA-1b in comparison with the control group of healthy blood donors. This difference was not significant and might have occurred by chance, since the allele frequencies of HPA-1b in all three groups assessed are within the range of published frequencies of HPA-1b in white populations (Table 3).

View this table: [in this window] [in a new window]   Table 3. HPA-1, HPA-2, HPA-3, and HPA-5 Allele Frequencies in Middle European Populations

Weiss et al² investigated the frequency of the HPA-1b genotype in 71 patients with myocardial infarct or unstable angina. They found a 2.1-fold higher frequency in patients than in the control group (myocardial infarct, 39.4% HPA-1ab and bb; control group, 19.1% HPA-1ab and bb). In a subgroup of 42 patients below the age of 60 years, the frequency of the HPA-1b allele was even more predominant (50%) compared with the control group (13.9%). However, Marian et al³ could not confirm the increased frequency of HPA-1b genotype in 180 patients with angiographically documented coronary artery disease. A third investigation on the same topic in 101 patients under the age of 60 years with a history of myocardial infarction was reported by Carter et al.⁴ They observed a nonsignificant trend toward a higher incidence of HPA-1b among their patients. Very recently, Ridker et al⁵ reported on the HPA-1 polymorphism in a subgroup of 704 men becoming symptomatic for myocardial infarction (n=375), stroke (n=209), or venous thrombosis (n=121) in a prospective cohort study (total of 14 916 initially healthy men). They did not find any association of the presence of the HPA-1b allele with an increase in subsequent risk of myocardial infarction, stroke, or venous thrombosis.

Currently, there is no explanation based on experimental data as to why the HPA-1b polymorphism of GPIIb/IIIa should be a risk factor for manifestation of arterial vessel occlusions.^{6 7} Thus far, there is only one preliminary report that platelets carrying the HPA-1b phenotype should bind less fibrinogen on activation with ADP compared with platelets with the HPA-1a phenotype.²⁶

Although we could not demonstrate any significant differences in the allele frequencies within the HPA-1, HPA-2, HPA-3, and HPA-5 polymorphisms in CVD patients compared with other neurological inpatients or healthy blood donors, we cannot exclude for certain that large studies might reveal an impact of these polymorphisms on the clinical outcome of patients with CVD.

	Acknowledgments

 
The study has been supported by the Deutsche Forschungsgemeinschaft GR 1096/2-2. This work is part of the Community Medicine Project and the Molecular Medicine Project of the Ernst-Moritz-Arndt-University, Greifswald, Germany. The technical assistance of A. Raether and G. Würtz is highly appreciated. We thank Dr K. Olbrich for her valuable pre-PCR work.

Received February 21, 1997; revision received April 18, 1997; accepted April 21, 1997.

	References

Top Abstract Introduction Subjects and Methods Results Discussion References

 
1. Newman PJ, Valentin N. Human platelet alloantigens: recent findings, new perspectives. Thromb Haemost. 1995;74:234-239.[Medline] [Order article via Infotrieve]

2. Weiss EJ, Bray PF, Tayback M, Schulman SP, Kickler TS, Becker LC, Weiss JL, Gerstenblith G, Goldschmidt-Clermont PJ. A polymorphism of a platelet glycoprotein receptor as an inherited risk factor for coronary thrombosis. N Engl J Med. 1996;334:1090-1094.[Abstract/Free Full Text]

3. Marian AJ, Brugada R, Kleiman NS. Platelet glycoprotein IIIa Pl^a polymorphism and myocardial infarction. N Engl J Med. 1996;335:1071-1072. Letter.[Free Full Text]

4. Carter AM, Ossei-Gerning N, Grant PJ. Platelet glycoprotein IIIa Pl^a polymorphism and myocardial infarction. N Engl J Med. 1996;335:1072-1073. Letter.

5. Ridker PM, Hennekens CH, Schmitz C, Stampfer MJ, Lindpaintner K. Pl^A1/A2 polymorphism of platelet glycoprotein IIIa and risks of myocardial infarction, stroke and venous thrombosis. Lancet. 1997;349:385-388.[Medline] [Order article via Infotrieve]

6. Nurden AT. Polymorphisms of platelet receptors as risk factors in coronary thrombosis. Eur Heart J. 1996;17:1293-1294.[Free Full Text]

7. Newman PJ. Platelet alloantigens: cardiovascular as well as immunological risk factors? Lancet. 1997;349:370-371. Commentary.[Medline] [Order article via Infotrieve]

8. Newman PJ, Derbes RS, Aster RH. The human platelet alloantigens, Pl^a1 and Pl^a2, are associated with a Leucine33/Proline33 amino acid polymorphism in membrane glycoprotein IIIa and are distinguishable by DNA typing. J Clin Invest. 1989;83:1778-1781.

9. Lyman S, Aster RH, Visentin GP, Newman PJ. Polymorphism of human platelet membrane glycoprotein IIb associated with the Bak^a/Bak^b alloantigen system. Blood. 1990;75:2343-2348.[Abstract/Free Full Text]

10. Kuijpers RWAM, Faber NM, Cuypers HTM, Ouwehand WH, von dem Borne AEGK. The N-terminal globular domain of the human platelet glycoprotein Iba has a methionine 145/threonine 145 amino acid polymorphism which is associated with the HPA-2 (Ko) alloantigens. J Clin Invest. 1992;89:381-384.

11. Mazzucato M, Pradella P, de Angelis V, Steffan A, de Marco L. Frequency and functional relevance of genetic threonin145/methionin145 dimorphism in platelet glycoprotein Iba in an Italian population. Transfusion. 1996;36:891-894.[Medline] [Order article via Infotrieve]

12. Santoso S, Kalb R, Walka M, Kiefel V, Mueller-Eckhardt C, Newman PJ. The human platelet alloantigens, Br^a and Br^b, are associated with a single amino acid polymorphism on glycoprotein Ia (integrin 2). J Clin Invest. 1993;92:2427-2432.

13. Kiefel V, Santoso S, Weisheit M, Mueller-Eckhardt C. Monoclonal antibody-specific immobilization of platelet antigens (MAIPA): a new tool for the identification of platelet-reactive antibodies. Blood. 1987;70:1722-1726.[Abstract/Free Full Text]

14. Liu LX, Nardi M, Flug F, Karpatkin S. Development of a monoclonal antibody capable of differentiating platelet Pl^A1/Pl^A1, Pl^A1/Pl^A2 and Pl^A2/Pl^A2 genotypes. Br J Haematol. 1992;81:113-117.[Medline] [Order article via Infotrieve]

15. Weiss EJ, Goldschmidt-Clermont PJ, Grigoryev D, Jin Y, Kickler TS, Bray PF. A monoclonal antibody (SZ21) specific for platelet GPIIIa distinguishes Pl^A1 from Pl^A2. Tissue Antigens. 1995;46:374-381.[Medline] [Order article via Infotrieve]

16. Griffin HM, Ouwehand WH. A human monoclonal antibody specific for the leucine-33 (Pl^a1, HPA-1a) form of platelet glycoprotein IIIa from a V gene phage display library. Blood. 1995;86:4430-4436.[Abstract/Free Full Text]

17. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16:1215.[Free Full Text]

18. Klüter H, Fehlau K, Panzer S, Kirchner H, Bein G. Rapid typing for human platelet antigen systems -1, -2, -3 and -5 by PCR amplification with sequence specific primers. Vox Sang. 1996;71:121-125.[Medline] [Order article via Infotrieve]

19. Bein G, Hackstein H, Klüter H. DNA typing of human antigen systems -1, -2, -3 and -5 in B-lymphoblastoid cell lines of the International Histocompatibility Workshop. Tissue Antigens. 1997;49:443-447.[Medline] [Order article via Infotrieve]

20. Harker LA. Clinical trials evaluating platelet-modifying drugs in patients with atherosclerotic cardiovascular disease and thrombosis. Circulation. 1986;73:206-223.[Abstract]

21. Antiplatelet Trialists' Collaboration. Collaborative overview of randomised trials of antiplatelet therapy, I: prevention of death, myocardial infarction and stroke by prolonged antiplatelet therapy in various categories of patients. BMJ. 1994;308:81-104.[Abstract/Free Full Text]

22. Bornstein NM, Karepov VG, Aronovich BD, Gorbulev AY, Treves TA, Korczyn AD. Failure of aspirin treatment after stroke. Stroke. 1994;25:275-277.[Abstract]

23. Unkelbach K, Kalb R, Santoso S, Kroll H, Mueller-Eckhardt C, Kiefel V. Genomic RFLP typing of human platelet alloantigens Zw(Pl^A), Ko, Bak and Br (HPA-1, 2, 3, 5). Br J Haematol. 1995;89:169-176.[Medline] [Order article via Infotrieve]

24. Legler TJ, Köhler M, Mayr WR, Panzer S, Ohto H, Fischer GF. Genotyping of the human platelet antigen systems 1 through 5 by multiplex polymerase chain reaction and ligaton-based typing. Transfusion. 1996;36:426-431.[Medline] [Order article via Infotrieve]

25. Holensteiner A, Walchshofer S, Adler A, Kittl E-M, Mayr WR, Panzer S. Human platelet antigen gene frequencies in the Austrian population. Haemostasis. 1995;25:133-136.[Medline] [Order article via Infotrieve]

26. Goldschmidt-Clermont PJ, Weiss EJ, Shear WS, Kennedy SD, Kickler T, Becker LC, Bray PF. Platelets from PL^A2(-) individuals bind more exogenous fibrinogen than platelets from PL^A2 (+) individuals. Blood Supply. 1996;88:26a. Abstract.

This article has been cited by other articles:

				T. CHIRAS, E. D. PAPADAKIS, A. KATOPODI, E. CHATZIANESTI, K. FOURTOUNAS, S. PAPAKONSTANTINOU, I. THEODOROPOULOS, A. DAKOURAS, N. ZEREFOS, D. VALIS, et al. Platelet GP IIIA Polymorphism HPA-1 (PLA1/2) Is Associated with Hypertension as the Primary Cause for End-stage Renal Disease in Hemodialysis Patients from Greece In Vivo, January 1, 2009; 23(1): 177 - 181. [Abstract] [Full Text] [PDF]

				J. M. Maguire, A. Thakkinstian, J. Sturm, C. Levi, L. Lincz, M. Parsons, S. Whyte, and J. Attia Polymorphisms in Platelet Glycoprotein 1b{alpha} and Factor VII and Risk of Ischemic Stroke: A Meta-Analysis Stroke, June 1, 2008; 39(6): 1710 - 1716. [Abstract] [Full Text] [PDF]

				J. P. Corsetti, D. Ryan, A. J. Moss, D. L. Rainwater, W. Zareba, and C. E. Sparks Glycoprotein Ib{alpha} Polymorphism T145M, Elevated Lipoprotein-Associated Phospholipase A2, and Hypertriglyceridemia Predict Risk for Recurrent Coronary Events in Diabetic Postinfarction Patients Diabetes, May 1, 2007; 56(5): 1429 - 1435. [Abstract] [Full Text] [PDF]

				N. K.J. Oksala, M. Heikkinen, J. Mikkelsson, T. Pohjasvaara, M. Kaste, T. Erkinjuntti, and P. J. Karhunen Smoking and the Platelet Fibrinogen Receptor Glycoprotein IIb/IIIA PlA1/A2 Polymorphism Interact in the Risk of Lacunar Stroke and Midterm Survival Stroke, January 1, 2007; 38(1): 50 - 55. [Abstract] [Full Text] [PDF]

				P. Kubisz, J. Ivankova, P. Holly, J. Stasko, and J. Musia/l The Glycoprotein IIIa PLA1/A2 Polymorphism--A Defect Responsible for the Sticky Platelet Syndrome? Clinical and Applied Thrombosis/Hemostasis, January 1, 2006; 12(1): 117 - 119. [PDF]

				J. P. Casas, A. D. Hingorani, L. E. Bautista, and P. Sharma Meta-analysis of Genetic Studies in Ischemic Stroke: Thirty-two Genes Involving Approximately 18 000 Cases and 58 000 Controls Arch Neurol, November 1, 2004; 61(11): 1652 - 1661. [Abstract] [Full Text] [PDF]

				K. Gwinn-Hardy and V. Dawson Genomics-Proteomics and Stroke: Introduction Stroke, November 1, 2004; 35(11_suppl_1): 2731 - 2734. [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]

				A. Slowik, T. Dziedzic, W. Turaj, J. Pera, L. Glodzik-Sobanska, P. Szermer, M. T. Malecki, D. A. Figlewicz, and A. Szczudlik A2 Alelle of GpIIIa Gene Is a Risk Factor for Stroke Caused by Large-Vessel Disease in Males Stroke, July 1, 2004; 35(7): 1589 - 1593. [Abstract] [Full Text] [PDF]

				R. D. McBane II Genetically Determined Procoagulant States and Heparin Use Seminars in Cardiothoracic and Vascular Anesthesia, December 1, 2003; 7(4): 427 - 442. [Abstract] [PDF]

				H. Ulrichts, K. Vanhoorelbeke, S. Cauwenberghs, S. Vauterin, H. Kroll, S. Santoso, and H. Deckmyn Von Willebrand Factor But Not {alpha}-Thrombin Binding to Platelet Glycoprotein Ib{alpha} Is Influenced by the HPA-2 Polymorphism Arterioscler Thromb Vasc Biol, July 1, 2003; 23(7): 1302 - 1307. [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]

				D. Feng, K. Lindpaintner, M. G. Larson, C. J. O'Donnell, I. Lipinska, P. A. Sutherland, M. Mittleman, J. E. Muller, R. B. D'Agostino, D. Levy, et al. Platelet Glycoprotein IIIa PlA Polymorphism, Fibrinogen, and Platelet Aggregability: The Framingham Heart Study Circulation, July 10, 2001; 104(2): 140 - 144. [Abstract] [Full Text] [PDF]

				R. I. Baker, J. Eikelboom, E. Lofthouse, N. Staples, V. Afshar-Kharghan, J. A. Lopez, Y. Shen, M. C. Berndt, and G. Hankey Platelet glycoprotein Ib{alpha} Kozak polymorphism is associated with an increased risk of ischemic stroke Blood, July 1, 2001; 98(1): 36 - 40. [Abstract] [Full Text] [PDF]

				J. S. Bennett, F. Catella-Lawson, A. R. Rut, G. Vilaire, W. Qi, S. C. Kapoor, S. Murphy, and G. A. FitzGerald Effect of the PlA2 alloantigen on the function of {beta}3-integrins in platelets Blood, May 15, 2001; 97(10): 3093 - 3099. [Abstract] [Full Text] [PDF]

				G.J. Hademenos, M.J. Alberts, I. Awad, M. Mayberg, T. Shephard, A. Jagoda, R.E. Latchaw, H.W. Todd, K. Viste, R. Starke, et al. Advances in the genetics of cerebrovascular disease and stroke Neurology, April 24, 2001; 56(8): 997 - 1008. [Abstract] [Full Text] [PDF]

				M. B. Frank, A. P. Reiner, S. M. Schwartz, P. N. Kumar, R. M. Pearce, P. G. Arbogast, W. T. Longstreth Jr, F. R. Rosendaal, B. M. Psaty, and D. S. Siscovick The Kozak sequence polymorphism of platelet glycoprotein Ib{alpha} and risk of nonfatal myocardial infarction and nonfatal stroke in young women Blood, February 15, 2001; 97(4): 875 - 879. [Abstract] [Full Text] [PDF]

				J. P. Mathew, C. S. Rinder, J. G. Howe, M. Fontes, J. Crouch, M. F. Newman, B. Phillips-Bute, and B. R. Smith Platelet PlA2 polymorphism enhances risk of neurocognitive decline after cardiopulmonary bypass Ann. Thorac. Surg., February 1, 2001; 71(2): 663 - 666. [Abstract] [Full Text] [PDF]

				T C F Sykes, C Fegan, and D Mosquera Thrombophilia, polymorphisms, and vascular disease Mol. Pathol., December 1, 2000; 53(6): 300 - 306. [Abstract] [Full Text]

				A. Hassan and H. S. Markus Genetics and ischaemic stroke Brain, September 1, 2000; 123(9): 1784 - 1812. [Abstract] [Full Text] [PDF]

				A. P. Reiner, P. N. Kumar, S. M. Schwartz, W. T. Longstreth Jr, R. M. Pearce, F. R. Rosendaal, B. M. Psaty, and D. S. Siscovick Genetic Variants of Platelet Glycoprotein Receptors and Risk of Stroke in Young Women Stroke, July 1, 2000; 31(7): 1628 - 1633. [Abstract] [Full Text] [PDF]

				D. A. Lane and P. J. Grant Role of hemostatic gene polymorphisms in venous and arterial thrombotic disease Blood, March 1, 2000; 95(5): 1517 - 1532. [Full Text] [PDF]

				A. Sonoda, M. Murata, D. Ito, N. Tanahashi, A. Ohta, Y. Tada, E. Takeshita, T. Yoshida, I. Saito, M. Yamamoto, et al. Association Between Platelet Glycoprotein Ib{alpha} Genotype and Ischemic Cerebrovascular Disease Stroke, February 1, 2000; 31(2): 493 - 497. [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]

				D. Feng, K. Lindpaintner, M. G. Larson, V. S. Rao, C. J. O'Donnell, I. Lipinska, C. Schmitz, P. A. Sutherland, H. Silbershatz, R. B. D'Agostino, et al. Increased Platelet Aggregability Associated With Platelet GPIIIa PlA2 Polymorphism : The Framingham Offspring Study Arterioscler Thromb Vasc Biol, April 1, 1999; 19(4): 1142 - 1147. [Abstract] [Full Text] [PDF]

				K. R. Wagner, W. H. Giles, C. J. Johnson, C.-Y. Ou, P. F. Bray, P. J. Goldschmidt-Clermont, J. B. Croft, V. K. Brown, B. J. Stern, B. R. Feeser, et al. Platelet Glycoprotein Receptor IIIa Polymorphism P1A2 and Ischemic Stroke Risk : The Stroke Prevention in Young Women Study Stroke, March 1, 1998; 29(3): 581 - 585. [Abstract] [Full Text] [PDF]

This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Carlsson, L. E. Articles by Kessler, C. Search for Related Content PubMed PubMed Citation Articles by Carlsson, L. E. Articles by Kessler, C.