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 Previous Article | Table of Contents | Next Article 
Blood, Vol. 93 No. 11 (June 1), 1999:
pp. 3583-3586
The  2 Gene Coding Sequence
T807/A873 of the Platelet Collagen
Receptor Integrin 2 1 Might Be a
Genetic Risk Factor for the Development of Stroke in Younger
Patients
By
Lena E. Carlsson,
Sentot Santoso,
Carsten Spitzer,
Christof Kessler, and
Andreas Greinacher
From the Departments of Immunology and Transfusion Medicine and of
Neurology, Ernst-Moritz-Arndt-University, Greifswald, Germany; and the
Department of Clinical Immunology and Transfusion Medicine,
Justus-Liebig-University, Giessen, Germany.
 |
ABSTRACT |
The polymorphisms C807T and G873A of the
platelet integrin  2 1 (collagen receptor
glycoprotein [GP] Ia-IIa) are linked to the expression density of
this receptor. The GPIa T807/A873 allele causes
a higher receptor expression, enhancing platelet binding to collagen.
This might present a genetic predisposition for the development of
thromboembolic complications. In this case-control study, the genotypes
of the GPIa C807T polymorphism and presence of conventional
risk factors (hypertension, diabetes mellitus, and smoking) were
compared in stroke patients and patients without cerebrovascular
disease (non-CVD patients)  50 years of age (n = 45 and 41, respectively) and in stroke patients and non-CVD patients more than 50 years of age (n = 182 and 129, respectively. In patients 50 years
of age, the T807 allele was the only overrepresented variable (P = .023; odds ratio, 3.02; 95% confidence
interval, 1.20 to 7.61) and an independent risk factor, whereas the
presence of conventional risk factors was similar between stroke
patients 50 years of age and non-CVD patients 50 years of age.
Large epidemiological studies should prove whether the platelet
collagen receptor GPIa-IIa T807 allele is an independent
risk factor for the development of stroke in younger patients.
© 1999 by The American Society of Hematology.
| |
INTRODUCTION |
THE DEVELOPMENT OF stroke is known to be
related to vascular risk factors such as hypertension, smoking,
diabetes mellitus,1,2 and possibly high
cholesterol.3 Besides these conventional risk factors,
genetic predispositions may enhance the risk of developing a
cerebrovascular thrombotic event.4-6 This is particularly true with stroke, as demonstrated by clustering of stroke cases in
certain families and by ethnic differences in stroke
incidence.7,8
Platelet-dependent thromboembolism is an underlying mechanism in the
pathogenesis of stroke. Several platelet receptors are known to be
polymorphic9; however, no platelet glycoprotein-receptor polymorphism has yet been associated with an increased risk for stroke.10
The platelet integrin  21, also known as
glycoprotein (GP) Ia-IIa, is one of the major collagen receptors
present on platelets.11 Via GPIa-IIa, platelets adhere to
collagen exposed in subendothelial structures and subsequently become
activated.12-14 Recently, two silent point mutations on
GPIa (2) were identified, C807T and G873A.15 These mutations were shown to be
associated with the expression density of GPIa-IIa on the platelet
surface,15 thus explaining the previously reported
difference in expression density of GPIa-IIa.16 The two
polymorphisms are linked with each other. GPIa
T807/A873 is associated with a higher
expression of the receptor and GPIa C807/G873
with a lower expression density.15 Furthermore, the
expression density of GPIa-IIa could be correlated to the rate of
platelet attachment to collagen type I, even under high shear
rates.17
The polymorphism increasing the density of GPIa-IIa on the surface of
platelets might present an inherited risk factor for platelet-dependent
thromboembolic complications. Studies in patients with myocardial
infarct18 and stroke4 indicate that genetic risk factors may be especially relevant to the development of arterial
vascular disease in younger patients. In this case-control study, we
assessed the GPIa C807T genotype distribution in 227 stroke
patients divided into different age groups (50 and >50 years of
age) and compared it with those of two control groups: inpatients
without cerebrovascular disease (non-CVD) and healthy blood donors.
| |
MATERIALS AND METHODS |
Study design and patients.
This case-control study was conducted in accordance with the good
clinical practice guidelines of the European community and the
Declaration of Helsinki. The study protocol was approved by the local
ethics committee of the University of Greifswald (Greifswald, Germany).
All patients and control subjects gave informed consent to participate
in the study.
Blood samples were collected from 227 stroke patients admitted to the
stroke service of the Department of Neurology. We included only
patients with focal neurological symptoms due to transient ischemic
attack or complete stroke and excluded patients with an intracerebral
or subarachnoidal hemorrhage. Patients with stroke resulting from
vasculitis or migraine were also excluded. All stroke patients
underwent ultrasound sonography (both extracranial and transcranial),
computed tomography (CT) or magnetic resonance imaging (MRI), and
electrocardiogram (ECG). Transesophageal echocardiography and digital
substraction angiography were optional. On the basis of clinical
features, CT/MRI findings, and cardiac diagnostic criteria, the
patients were assigned to the following CVD categories: (1)
large-vessel disease stroke due to significant (>70%) stenosis of
the extracranial symptomatic artery; (2) lacunar strokedue to small
deep infarctions, with the location of the lacunae seen in the CT/MRI
matched to the clinical symptoms; (3) cardiac embolismsource positively diagnosed by ECG or transesophageal echocardiography; or (4)
othereg, arterial dissection or unknown pathogenesis despite intensive investigation.
The stroke patients were compared with a control group of 170 neurological inpatients showing no acute or recent signs of CVD or any
other condition in which vascular pathology plays a major role, such as
migraine or arteriovenous malformations. Further exclusion criteria for
the control group were acute myocardial infarction or venous thrombosis.
A second control group of 184 healthy blood donors was assessed to
establish the GPIa-IIa C807T allele distribution in the regional population. All participants were whites living in the same
geographical region.
DNA preparation and genotyping.
DNA was prepared from 5 mL whole blood according to Miller et
al19 or from 250 µL buffy coat with the QIAamp blood kit
(Qiagen GmbH, Hilden, Germany). Genotyping was performed in accordance with a newly developed sequence-specific primer (SSP)-polymerase chain
reaction (PCR) method.20 In brief, 5 µL genomic DNA (20 µg/mL) was added to a 50 µL reaction mixture containing 10 mmol/L Tris (pH 8.3), 50 mmol/L KCl, 1.5 mmol/L MgCl2, 0.125 mmol/L dNTP, 0.25 µmol/L each of sense primer #92V (5'-GAC AGC
CCA TTA ATA AAT GTC TCC TCT G) and sequence-specific antisense primer
#96C (5'-CCT TGC ATA TTG AAT TGC TAC G) or #96T (5'-CCT TGC
ATA TTG AAT TGC TAC A), 0.125 µmol/L each of internal control primers HGH I (5'-CAG TGC CTT CCC AAC CAT TCC CTT A) and HGH II
(5'-ATC CAC TCA CGG ATT TCT GTT GTG TTT C), and 2.5 U TaqGold
(Perkin Elmer, Vaterstetten, Germany). After initial denaturation at
96°C for 10 minutes, 35 cycles of amplification were performed
(93°C for 50 seconds, 56°C for 30 seconds, and 72°C for 15 seconds). The PCR products were analyzed on 1.5% agarose gels and
visualized by ethidium bromide staining.
Statistical analyses.
The allele frequencies and genotypes determined for stroke patients,
non-CVD patients, and blood donors were compared by  2
analysis in 2 × 2 and 3 × 2 fields, respectively. Fisher's
exact test in 2 × 2 fields was used to compare other nominal
data. The significance level was established at P .05. Odds
ratios with the corresponding 95% confidence interval (CI) were
determined for conventional risk factors (hypertension, diabetes,
smoking [current or ex-smoker], and high cholesterol [defined as
known high levels of plasma cholesterol, current lipid-lowering
medication use, and/ or plasma cholesterol  6.5 mmol/L]), positive
family history (stroke), and the presence of the GPIa T807
allele. The statistical analyses were performed using SAS software (SAS
Institute, Cary, NC). A logistic regression analysis
performed on SPSS software (SPSS Inc, Chicago, IL)
included gender, hypertension, diabetes mellitus, smoking, high
cholesterol, and the GPIa genotype in the age-defined patient groups.
| |
RESULTS |
Patient/control subject characteristics.
The 227 stroke patients included 107 men (47.1%) and 120 women
(52.9%). Their mean age was 62.2 ± 14.3 years. The control group
of 170 neurological non-CVD inpatients comprised 78 men (45.9%) and 92 women (54.1%) with a mean age of 59.4 ± 14.3 years. Forty-five
stroke patients (19.8%) and 41 non-CVD patients (24.1%) were 50
years of age. Patients' and control subjects' characteristics are
shown in Table 1. One hundred and
eighty-four healthy blood donors (104 men and 80 women) were included
in the study to reflect the GPIa C807T genotype
distribution in a Middle European population. Their mean age was 30.3 ± 7.1 years.
Forty-two patients (18.5%) presented with a transient ischemic
attack and 185 patients (81.5%) suffered a complete stroke. In the
stroke patients, the pathogenesis were large vessel atherosclerosis in
70 patients (30.8%), lacunar stroke in 34 patients (15%), and cardiac
embolic sources in 53 patients (23.3%). More than one of these causes
was found in 16 patients (7%), 12 (5.3%) participants suffered from a
dissection, and the pathogenesis of stroke remained unknown in 42 patients (18.5%).
GPIa C807T allele frequencies, genotype distributions,
and conventional risk factors in stroke patients, non-CVD patients, and
healthy blood donors.
There were no differences between non-CVD patients and healthy blood
donors in GPIa C807T allele frequencies (0.59 C807, 0.41 T807 v 0.61 C807, 0.39 T807, respectively; P = .53)
and genotype distributions (34.1% CC807, 48.8%
CT807, 17.1% TT807 v 37.5%
CC807, 46.7% CT807, 15.8% TT807,
respectively; P = .8).
The distribution of predefined risk factors, as well as the proposed
risk factor, GPIa T807, were compared between (1) stroke patients (n = 45) and non-CVD patients (n = 41) 50 years of age and
(2) stroke patients (n = 182) and non-CVD patients (n = 129) more than
50 years of age (Table 1). In the group 50 years of age, none of the
conventional risk factors was overrepresented in stroke patients. The
only difference between the groups of patients 50 years of age was
the overrepresentation of GPIa T807 in stroke patients
(odds ratio, 3.02; 95% CI, 1.20 to 7.61). In contrast, in the patient
group more than 50 years of age, hypertension (P < .001),
diabetes mellitus (P = .009), and smoking (P = .001) were overrepresented in stroke patients compared with non-CVD patients.
High cholesterol (P = 1.000), a positive family history (P = .767), and GPIa T807 (P = .712) were
not overrepresented in the group of older stroke patients compared with
control patients (Table 1).
A logistic regression model (Table 2)
confirmed the importance of the GPIa T807 allele in the
young stroke patients. The presence of GPIa T807 was
identified as the only independent risk factor in this group (P = .0207). In contrast, in the patient group >50 years of age,
hypertension (P < .0001), diabetes (P = .0110), and smoking (P = .0075) were independent risk
factors for stroke.
A comparison of stroke pathogenesis in younger and older CVD patients
is presented in Table 3. There were no
lacunar strokes in younger patients, but dissection and unknown
pathogenesis were more frequent in this group than in the older
patients. The genotype distribution relative to CVD pathogenesis is
also given in Table 3. The GPIa T807 allele was
most frequent in young CVD patients with stroke due to carotid
atherosclerosis (86%) or due to cardiac embolic sources (100%).
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|
Table 3.
Comparison of Stroke Pathogenesis and the Presence of
the GPIa T807 Allele in Stroke Patients 50 Years and
>50 Years of Age
|
|
In stroke patients with a positive family history, 27 of 41 (65.8%)
carried the GPIa T807 allele, but 64 of 92 (70.0%) of the
stroke patients without strokes in the family history also carried the
GPIa T807 allele (P = .69). Of stroke patients 50 years of age, the family history was available in 25 cases, and 7 of
these had a positive family history. Of the 7 with positive family
histories, 5 (71.4%) carried the GPIa T807 allele. Of the remaining 18 stroke patients 50 years of age without a positive family history, 12 (66.7%) also carried the GPIa T807 allele.
| |
DISCUSSION |
Results of this pilot case-control study show that the polymorphism
T807/A873 of the 2 gene coding
sequence of platelet integrin 21, also
known as GPIa-IIa, may be an inherited risk factor for the development
of stroke in patients 50 years of age (odds ratio, 3.02; 95% CI,
1.20 to 7.61).
Platelet adhesion to subendothelial tissue is largely mediated via the
collagen receptor GPIa-IIa.11 The GPIa gene is polymorphic at position 807 (C-T) and this point mutation is
associated with GPIa-IIa expression density on the platelet surface.
Platelets from individuals homozygous or heterozygous for the GPIa
T807 allele show an increased expression of GPIa-IIa;
consequently, an enhanced adhesion to collagen compared with platelets
homozygous for GPIa C807.15-17
In patients 50 years of age, GPIa T807 was the only
significant predefined risk factor for stroke; moreover, logistic
regression analysis showed GPIa T807 to be an independent
risk factor for stroke in this patient group. However, the effect of
the GPIa T807 allele as a risk factor for stroke was not
pronounced, which may be due to the small number of patients in our
pilot study. Nevertheless, this effect might be important for subgroups
of stroke patients, because the GPIa T807 allele was
particularly prominent in younger patients who had a stroke due to
carotid atherosclerosis or cardiac embolism (Table 2). In fact, all
patients 50 years of age who suffered a stroke likely due to cardiac
embolism carried the GPIa T807 allele. In patients more
than 50 years of age, the GPIa T807 allele was not as
frequent and its potential effect appears to be overshadowed by
conventional risk factors and general vessel disease.
Atherosclerosis is usually less frequent in younger patients than in
older ones, but in our study 31% of the stroke patients 50 years of
age and 31% of stroke patients more than 50 years of age presented
with carotid artery atherosclerosis. Unfortunately, we could not
calculate the effect of this risk factor in the multiple regression
analysis model because patients in the control group were not
systematically assessed for atherosclerosis of the carotid artery.
Surprisingly, we found no clear correlation between the presence of the
GPIa T807 allele and a positive family history of CVD,
which one would expect with a genetic risk factor. Again, this finding
might be related to the small sample size of the study.
Results of this pilot study concur with findings of Santoso et al
(manuscript submitted), who investigated the impact of
GPIa C807T polymorphism on the development of coronary
artery disease and myocardial infarction. These investigators assessed
2,237 male patients admitted for angiography and identified a strong association of the GPIa T807 allele with nonfatal
myocardial infarction in younger patients.20 Conversely, if
the presence of the GPIa T807 allele is a potential
thromboembolic risk factor, the C807 allele may be
associated with an increased bleeding risk in certain populations.
DiPaola et al22 found an overrepresentation of the GPIa
C807 allele among type I von Willebrand's disease patients with bleeding complications.
Although there is increasing evidence that the GPIa T807
allele is an important genetic factor in the predisposition for
thromboembolic events, due to the small number of patients in this
pilot case-control study, our findings remain preliminary and require
confirmation by larger epidemiological studies. Such studies could
provide a rationale for determining the GPIa C807T
polymorphism to stratify at-risk patients for different antiplatelet
treatments. Furthermore, GPIa-IIa itself might be an interesting target
for long-term pharmacologic inhibitors of platelet function in
high-risk patient populations.
| |
ACKNOWLEDGMENT |
The skillful technical assistance work of C. Blumentritt and the
biometric advice of Dr B. Jäger and Dr M. Wodny are highly appreciated. We thank Prof Dr R. Walther for support in purification of
patient DNA. The study is part of the Community Medicine program of the
Medical Faculty of the Ernst-Moritz-Arndt-University Greifswald. The
language editorial help of S. Owens is appreciated.
| |
FOOTNOTES |
Submitted September 4, 1998; accepted January 11, 1999.
Supported by the Deutsche Forschungsgemeinschaft Gr1096/2-2.
The publication costs of this
article were defrayed in part by
page charge payment. This article
must therefore be hereby marked
"advertisement"
in accordance with 18 U.S.C. section
1734 solely to indicate this fact.
Address reprint requests to Andreas Greinacher, MD,
Department of Immunology and Transfusion Medicine,
Ernst-Moritz-Arndt-University, Sauerbruchstr., D-17487 Greifswald,
Germany; e-mail: greinach{at}uni-greifswald.de.
| |
REFERENCES |
1.
Kanter MC, Sherman DG:
Strategies for preventing stroke.
Curr Opin Neurol Neurosurg
6:60, 1993[Medline]
[Order article via Infotrieve]
2.
Khaw KT:
Epidemiology of stroke.
J Neurol Neurosurg Psychiatry
61:333, 1996[Free Full Text]
3.
Prospective studies collaboration:
Cholesterol, diastolic blood pressure, and stroke: 13,000 strokes in 450,000 people in 45 prospective cohorts.
Lancet
346:1647, 1995[Medline]
[Order article via Infotrieve]
4.
Kiely DK, Wolf PA, Cupples LA, Beiser AS, Myrs RH:
Familial aggregation of stroke: The Framingham study.
Stroke
24:1366, 1993[Abstract/Free Full Text]
5.
Graffagnino C, Gasecki AP, Doig GS, Hachinski VC:
The importance of family history in cerebrovascular disease.
Stroke
25:599, 1994
6.
Pullicino P, Greenberg S, Trevisan M:
Genetic stroke risk factors.
Curr Opin Neurol
10:58, 1997[Medline]
[Order article via Infotrieve]
7.
Howard G, Anderson R, Sorlie P, Andrews V, Backlund E, Burke GL:
Ethnic differences in stroke mortality between non-Hispanic whites, Hispanic whites, and blacks. The national longitudinal mortality study.
Stroke
25:2120, 1994[Abstract]
8.
Morgenstern LB, Spears WD, Goff DC, Grotta JC, Nichaman MZ:
African Americans and women have the highest stroke mortality in Texas.
Stroke
28:15, 1997[Abstract/Free Full Text]
9.
Santoso S, Kiefel V:
Human-platelet specific alloantigen: Update.
Vox Sang
74:249, 1998 (suppl 2)
10.
Carlsson LE, Greinacher A, Spitzer C, Walther R, Kessler C:
Polymorphisms of the human platelet antigens HPA-1, HPA-2, HPA-3, and HPA-5 on the platelet receptors for fibrinogen (GP IIb/IIIa), von Willebrand factor (GP Ib/IX), and collagen (GPIa/IIa) are not correlated with an increased risk for stroke.
Stroke
28:1392, 1997[Abstract/Free Full Text]
11.
Santoro SA, Zutter MM:
The 21 integrin: A collagen receptor on platelets and other cells.
Thromb Haemost
74:813, 1995[Medline]
[Order article via Infotrieve]
12.
Nieuwenhuis HK, Akkerman JWN, Houdijk WPM, Sixma JJ:
Human blood platelets showing no response to collagen fail to express surface glycoprotein Ia.
Nature
318:470, 1985[Medline]
[Order article via Infotrieve]
13.
Kehrel B, Balleisen L, Kokott R, Mesters R, Stenzinger W, Clementson KJ, van de Loo J:
Deficiency of intact thrombospondin and membrane glycoprotein Ia in platelets with defective collagen-induced aggregation and spontaneous loss of disorder.
Blood
71:1074, 1988[Abstract/Free Full Text]
14.
Handa M, Watanabe K, Kawai Y, Kamata T, Koyama T, Nagai H, Ikeda Y:
Platelet unresponsiveness to collagen: Involvement of glycoprotein Ia-IIa (21 integrin) deficiency associated with a myeloproliferative disorder.
Thromb Haemost
73:521, 1995[Medline]
[Order article via Infotrieve]
15.
Kunicki TJ, Kritzik M, Annis DS, Nugent DJ:
Hereditary variation in platelet integrin 21 density is associated with two silent polymorphisms in the 2 gene coding sequence.
Blood
89:1939, 1997[Abstract/Free Full Text]
16.
Kunicki TJ, Orchekowski R, Annis D, Honda Y:
Variability of integrin 21 activity on human platelets.
Blood
82:2693, 1993[Abstract/Free Full Text]
17.
Kritzik M, Savage B, Nugent DJ, Santoso S, Ruggeri ZM, Kunicki TJ:
Nucleotide polymorphisms in the 2 gene define multiple alleles that are associated with differences in platelet 21 density.
Blood
92:2382, 1998[Abstract/Free Full Text]
18.
Hoit BD, Gilpin EA, Henning H, Maisel AA, Dittrich H, Carlisle J, Ross J:
Myocardial infarction in young patients: an analysis by age subsets.
Circulation
74:712, 1986[Abstract/Free Full Text]
19.
Miller SA, Dykes DD, Polesky HF:
A simple salting out procedure for extracting DNA from human nucleated cells.
Nucleic Acids Res
16:1215, 1988[Free Full Text]
20. Santoso S, Kunicki TJ, Kroll H, Haberbosch W, Gardemann A:
Association of the platelet glycoprotein Ia C807T gene
polymorphism with nonfatal myocardial infarction in younger patients.
Blood (in press)
21.
Moshfegh K, Wuillemin WA, Redondo M, Lammle B, Beer JH, Liechti-Gallati S, Meyer BJ:
Association of two silent polymorphisms of the platelet glycoprotein Ia/IIa receptor with risk of myocardial infarction: A case-control study.
Lancet
353:351, 1999[Medline]
[Order article via Infotrieve]
22.
DiPaola J, Federici AB, Sacchi E, Canciani MT, Mannucci PM, Kritzik M, Kunicki T, Nugent D:
Low platelet 21 levels in patients with von Willebrand disease type I represents an increased risk factor for bleeding.
Blood
90:27a, 1997 (abstr, suppl 1)
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|
Z. Wang, T. M. Leisner, and L. V. Parise
Platelet {alpha}2{beta}1 integrin activation: contribution of ligand internalization and the {alpha}2-cytoplasmic domain
Blood,
August 15, 2003;
102(4):
1307 - 1315.
[Abstract]
[Full Text]
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B. Nieswandt and S. P. Watson
Platelet-collagen interaction: is GPVI the central receptor?
Blood,
July 15, 2003;
102(2):
449 - 461.
[Abstract]
[Full Text]
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L. Pontiggia, R. Lassila, S. Pederiva, H.-R. Schmid, M. Burger, and J. H. Beer
Increased Platelet-Collagen Interaction Associated With Double Homozygosity for Receptor Polymorphisms of Platelet GPIa and GPIIIa
Arterioscler Thromb Vasc Biol,
December 1, 2002;
22(12):
2093 - 2098.
[Abstract]
[Full Text]
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C. Muckian, A. Fitzgerald, A. O'Neill, A. O'Byrne, D. J. Fitzgerald, and D. C. Shields
Genetic variability in the extracellular matrix as a determinant of cardiovascular risk: association of type III collagen COL3A1 polymorphisms with coronary artery disease
Blood,
July 30, 2002;
100(4):
1220 - 1223.
[Abstract]
[Full Text]
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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]
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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]
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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]
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J.Y. Streifler, N. Rosenberg, A. Chetrit, R. Eskaraev, B.A. Sela, R. Dardik, A. Zivelin, B. Ravid, J. Davidson, U. Seligsohn, et al.
Cerebrovascular Events in Patients With Significant Stenosis of the Carotid Artery Are Associated With Hyperhomocysteinemia and Platelet Antigen-1 (Leu33Pro) Polymorphism
Stroke,
December 1, 2001;
32(12):
2753 - 2758.
[Abstract]
[Full Text]
[PDF]
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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]
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W. J. Jones, L. S. Williams, and J. F. Meschia
Validating the Questionnaire for Verifying Stroke-Free Status (QVSFS) by Neurological History and Examination
Stroke,
October 1, 2001;
32(10):
2232 - 2236.
[Abstract]
[Full Text]
[PDF]
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T. J. Kunicki and Z. M. Ruggeri
Platelet Collagen Receptors and Risk Prediction in Stroke and Coronary Artery Disease
Circulation,
September 25, 2001;
104(13):
1451 - 1453.
[Full Text]
[PDF]
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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]
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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]
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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]
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A. Hassan and H. S. Markus
Genetics and ischaemic stroke
Brain,
September 1, 2000;
123(9):
1784 - 1812.
[Abstract]
[Full Text]
[PDF]
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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]
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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]
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E. Arnaud, V. Barbalat, V. Nicaud, F. Cambien, A. Evans, C. Morrison, D. Arveiler, G. Luc, J.-B. Ruidavets, J. Emmerich, et al.
Polymorphisms in the 5' Regulatory Region of the Tissue Factor Gene and the Risk of Myocardial Infarction and Venous Thromboembolism : The ECTIM and PATHROS Studies
Arterioscler Thromb Vasc Biol,
March 1, 2000;
20(3):
892 - 898.
[Abstract]
[Full Text]
[PDF]
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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]
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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]
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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]
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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]
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M. Achison, C. M. Elton, P. G. Hargreaves, C. G. Knight, M. J. Barnes, and R. W. Farndale
Integrin-independent Tyrosine Phosphorylation of p125fak in Human Platelets Stimulated by Collagen
J. Biol. Chem.,
January 26, 2001;
276(5):
3167 - 3174.
[Abstract]
[Full Text]
[PDF]
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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. Chem.,
June 22, 2001;
276(26):
23518 - 23524.
[Abstract]
[Full Text]
[PDF]
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H. Chen, D. Locke, Y. Liu, C. Liu, and M. L. Kahn
The Platelet Receptor GPVI Mediates Both Adhesion and Signaling Responses to Collagen in a Receptor Density-dependent Fashion
J. Biol. Chem.,
January 18, 2002;
277(4):
3011 - 3019.
[Abstract]
[Full Text]
[PDF]
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TOP
ABSTRACT
INTRODUCTION