(Circulation. 2000;102:1901.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Platelet PlA2 Allele and Incidence of Coronary Heart Disease
Results From the Atherosclerosis Risk In Communities (ARIC) Study
From the Division of Hematology and Vascular Biology Research Center, University of Texas-Houston Medical School, Houston, Tex (N.A., H.J., C.A., K.K.W.); the Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis (A.R.F.); Human Genetics Center, University of Texas-Houston Health Science Center, Houston, Tex (E.B.); and the Department of Biostatistics, University of North Carolina, Chapel Hill (L.E.C.).
Correspondence to Kenneth K. Wu, MD, PhD, Division of Hematology, University of Texas-Houston Medical School, 6431 Fannin, MSB 5.016, Houston, TX 77030. E-mail Kenneth.K.Wu{at}uth.tmc.edu
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Background—The major platelet integrin glycoprotein IIb-IIIa plays a primary role in platelet aggregation and acute thrombus formation at the site of vascular injury. A genetic polymorphism of glycoprotein IIb-IIIa (PlA) has recently been proposed as a potential genetic factor linking to platelet hyperaggregability and increased risk of myocardial infarction. Despite numerous, mostly nonprospective studies, the role of this polymorphism as a clinically relevant, inherited risk factor for coronary heart disease (CHD) is still controversial. The purpose of this study was to determine whether PlA2 is a risk factor for incident CHD and whether it is correlated with increased platelet activation in a case-cohort study nested within a prospective epidemiologic investigation.
Methods and Results—Blood samples were collected and processed from the Atherosclerosis Risk in Communities Study cohort at the baseline examination (1987 to 1989). They were stored at -80°C. PlA1/A2 genotype and plasma ß-thromboglobulin levels were determined in 439 incident CHD cases and a reference cohort sample of 544 (of whom 18 were also CHD cases). The prevalence of the PlA2 allele was not different in cases versus noncases. No significant correlation between CHD risk factors and the PlA2 allele was noted either. Platelet activation, as measured by plasma ß-thromboglobulin levels, was not enhanced in individuals with the PlA2 allele.
Conclusions—This prospective study indicates that healthy individuals carrying the PlA2 allele do not have an increased risk of CHD.
Key Words: platelets • glycoproteins • coronary disease
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Platelet activation and aggregation play key roles in the process of arterial thrombosis.1 Successful prevention of arterial thrombotic events with inhibitors of platelet aggregation underscores the critical role that platelet aggregation plays in human arterial thrombotic disorders. Aspirin, which blocks platelet thromboxane A2 synthesis, thereby suppressing platelet aggregation, is efficacious in preventing coronary heart disease (CHD) and thrombotic stroke.2 Abciximab and other antagonists of fibrinogen binding to glycoprotein (GP)IIb-IIIa have been shown to reduce thrombotic complications after coronary angioplasty or atherectomy.3
Platelet hyperaggregability has often been detected in patients with myocardial infarction (MI).1 Prospective studies further indicate that increased platelet aggregability is an independent risk factor for recurrent MI.4 The mechanism by which platelet hyperaggregability arises is unclear, but both genetic and environmental factors probably contribute.5 6 The genetic polymorphism of GPIIb-IIIa has recently been proposed as a potential factor related to platelet hyperaggregability and increased risk of MI.7 8 Binding of fibrinogen and von Willebrand factor to GPIIb-IIIa is the final common pathway by which platelet aggregation occurs.9 Hence, GPIIb-IIIa occupies a pivotal position in platelet aggregation. A number of polymorphisms have been identified for the GPIIb and GPIIIa genes. A GPIIIa polymorphism at codon 33 (Leu33Pro), also known as PlA1/A2 (or HPA-1a and HPA-1b), was reported by Weiss et al7 to be associated with acute MI. They reported in a case-control study that the frequency of the GPIIIa Pro33 allele was increased in MI cases. Several other case-control studies have been reported, but the results are inconsistent.10 11 12 13 The purpose of this study was to determine whether PlA2 is a risk factor for incident CHD and whether it is related to increased platelet activation in a prospective case-cohort study within the Atherosclerosis Risk in Communities (ARIC) Study cohort.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Study Population
In 1987 through 1989, the ARIC study recruited a population-based cohort of men and women 45 to 64 years of age from 4 US communities. Details of the criteria for inclusion of subjects from the participating communities and relevant epidemiologic data have been presented elsewhere.14 A total of 15 792 participants completed a home interview and clinic examination. Since enrollment, the subjects in this cohort have been prospectively followed for development of CHD and other vascular events. Participants were contacted annually by telephone to identify all hospitalizations and deaths. Death certificates and discharge lists from local hospitals from ARIC surveillance are also reviewed on a continuous basis to detect events occurring to cohort participants.
Ascertainment of Incident CHD Cases
For the present study, we included all CHD events occurring
between ARIC visit 1 (1986 to 1988) and December 31, 1993. The mean
follow-up time was 6.2 years and the standard error of the mean was 0.1
years. We defined CHD incidence as (1) a definite or probable MI, (2) a
silent MI between examinations detectable by ECG, (3) a definite fatal
CHD death, or (4) a coronary
revascularization. The ascertainments of CHD cases
and criteria for CHD classification have been previously
described.15
Baseline Measurements
The definitions and methods used for baseline measurements
(systolic blood pressure, hypertension, diabetes mellitus,
alcohol intake, plasma total cholesterol,
triglycerides, HDL-cholesterol,
LDL-cholesterol, fibrinogen) were published
elsewhere.16
Determination of PlA Genotypes
PlA1/A2 genotype was
analyzed by polymerase chain reaction (PCR) and restriction
fragment length polymorphism, according to a previously published
procedure.7 A 266-bp DNA fragment containing exon 2 was
amplified by PCR with primers flanking the exon. The PCR products
were digested separately with 2 restriction enzymes, MspI
and NciI, (New England Biolabs, Beverly, Mass), and the
resulting fragments were visualized and typed after electrophoresis on
a 3% agarose gel and staining. A new restriction site is generated as
the result of the PlA2 polymorphism. We did a
blind replicate DNA analysis for genotyping the
PlA polymorphism. Results from replicate pair
analysis (n=45) showed that the 
value was 0.939, which
indicates very strong agreement between blind duplicates in determining
the PlA polymorphism.
Plasma ß-Thromboglobulin Assay
Blood samples were collected and processed according to
standardized procedures and organizational plans described
previously.17 Plasma level of
ß-thromboglobulin (ß-TG) was determined by an
ELISA assay with kits obtained from American Bioproducts. The
ß-TG assay has a coefficient of variation of 6.8% and a reliability
coefficient of 0.83.18
Cohort Sample
We used a case-cohort design for the present study in which
information on GPIIIa Leu33Pro polymorphism and plasma ß-TG was
determined only for incident CHD cases and a stratified random sample
of the ARIC cohort. In our case-cohort sampling, all the incident cases
were included, along with a random sample from the full cohort,
including a random few incident cases in the later. The model-fitting
procedures account for some cases being so selected into the cohort
random sample.19 For the reference cohort, we stratified
the sampling by age (2 groups), sex, and average carotid far-wall
intima-media thickness measurements at baseline (thin: <30th
percentile; not thin: >30th percentile), oversampling those with thin
walls. We calculated means and proportions on several variables for
the entire cohort without prevalent disease (cohort, n=14 291), the
cohort random sample (CRS, n=544), and cohort random sample plus CHD
cases (CRS+CHD, n=965) primarily to determine the similarities in
demographics. The mean follow-up times were 2241 days, 2262 days, and
2249 days for cohort, CRS+CHD, and CRS, respectively. Percentages of
blacks were 27.1, 25.3, and 24.7, respectively, and percentages of men
were 43.2, 43.2, and 43.3, respectively, for cohort, CRS+CHD, and
CRS.
Exclusions
We excluded participants with prevalent CHD, stroke, or
transient ischemic attack. We also excluded very few
participants who were neither white nor black. A total of 997
participants were in the cohort random sample or had CHD before
December 31, 1993. Of these, 32 were excluded for missing GPIIIa
results, because of either a missing DNA sample or failure of the PCR
amplification. The final sample contained 965 individuals. The sample
included 439 CHD cases and a reference cohort sample of 544 (of whom 18
were also CHD cases). For the purpose of correlating plasma level of
ß-TG with GPIIIa genotype, only 795 participants who had
results for both GPIIIa genotype and plasma level of ß-TG
were analyzed.
Statistical Analysis
For data analysis, we combined A1A2 and A2A2 and
compared them with A1A1 because the prevalence of A2A2 was very low.
Therefore, the genetic model is one that considers A2 dominant over A1.
To determine the relation of GPIIIa PlA1/A2
polymorphism with other variables, including ß-TG, some of
which may be confounders in this analysis, we used ANCOVA to
compute age-, race-, and sex-adjusted mean levels or percentages of the
other variables for A1A2/A2A2 and A1A1. We also used ANCOVA to
compute age-, race-, and sex-adjusted mean levels or percentage values
of study variables for CHD cases versus noncases after appropriate
weighting for the stratified case-cohort sampling design. For this
descriptive analysis, we treated the cases as 1 stratum and
divided the noncases into 8 strata as described for the cohort sample
and weighted each stratum by the inverse of the sampling fraction. We
computed the risk ratios and 95% confidence intervals for the time to
the development of CHD by using a weighted, proportional hazards
regression by Barlow’s method.19 In the weighted,
proportional hazards regression models, we adjusted GPIIIa
PlA1/A2 estimates for sex, age, race, and other
factors related to CHD in this sample: hypertension, diabetes mellitus,
total cholesterol, HDL-cholesterol,
LDL-cholesterol, fibrinogen, smoking, and ethanol
intake.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Since the proportion of the PlA2/A2 genotype was too small (<2%) to determine its independent risk for CHD, the A1A2 heterozygotes and A2A2 homozygotes were combined for data analysis. The frequency of the A1A1 genotype in cases was 73.1% as compared with 74.1% in noncases, and the A1A2+A2A2 frequency was 26.9% in cases as compared with 25.9% in noncases (Table 1
). These
differences were not statistically significant (P=0.79).
There was no difference in genotype distribution between whites
and blacks.
|
As previously reported, there was a higher proportion of risk factors
(systolic blood pressure, total cholesterol, total
triglyceride, cigarette smoking, hypertension and diabetes
mellitus, P<0.001 for each) in our cases than in noncases.
The cases were older than noncases (56.2 versus 53.8 years,
P<0.0001), and there were more men in cases than noncases
(70.8% versus 42.2%, P<0.0001). The proportion of blacks
was not significantly different between cases and noncases (26.6%
versus 25.1%, P=0.7). There was no statistically
significant difference in the genotype frequency between cases
versus noncases within and between the two races (Table 1
).
PlA1 and PlA2 allele
frequencies were also not significantly different between cases and
noncases (P=0.91) within and between the two races after
adjusting for the confounding effects of age, race, and sex; 69.5% of
our incident cases had acute coronary syndrome, whereas the
remaining 30.5% had silent MI or severe coronary
stenosis requiring coronary
revascularization. When the latter was excluded
from analysis, the difference in PlA1
alleles between cases and noncases remained statistically
insignificant.
To exclude possible false-negative results, we determined the minimal
detectable difference in A1A1 prevalence between cases and noncases by
a 2-sided 
2 test. The minimal detectable
difference was 18%, given an 
error of 0.05 and a ß error of 0.2,
based on the case (n=439) and noncase (n=521) size and the observed
A1A1 frequency in noncases (74.1%). Thus, we should be able to detect
a difference of 18% in A1A1 prevalence between cases and noncases. Our
finding of an insignificant difference in A1 and A2 alleles between
cases and noncases is not due to false-negative results.
Table 2 shows the characteristics of the
cohort reference subjects with respect to the presence or absence of
the PlA2 allele. There was no significant
difference in any of the variables considered. The weighted,
proportional hazards regression analysis showed that
PlA2 genotype was not significantly
associated with the time to development of CHD after controlling for
potentially confounding effects of other risk factors such as age, sex,
ethnic background, hypertension, diabetes mellitus, total
cholesterol, total triglycerides, HDL-C,
fibrinogen, and smoking (RR=1.37; 95% CI=0.89 to 2.11).
|
In noncases there was no significant difference in age-, race-, and
sex-adjusted mean plasma ß-TG values between participants with the
A1A1 genotype (22.6 ng/mL) and individuals with the A1A2+A2A2
genotypes (18.7 ng/mL, P=0.797)
(Figure). Likewise, for CHD cases, the
age-, race-, and sex-adjusted mean values of ß-TG were similar: 22.1
ng/mL for A1A1 and 21.6 ng/mL for A1A2/A2A2 (P=0.667).
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
We found no increase in risk of incident CHD in individuals heterozygous or homozygous for the PlA2 allele in our community-based, prospective, case-cohort study. Previous reports have provided contradictory information. A case-control study by Weiss et al7 suggested an association between acute MI and the PlA2 allele. This association was stronger in patients <60 years of age when compared with those >60 years of age. Similar findings were reported in another large nonprospective study involving 405 white patients who underwent angiography for investigation of chest pain or suspected coronary artery disease.11 In another study, acute MI with multiple-vessel atherosclerotic disease was associated significantly with the PlA2 allele, but an association between the extent of coronary artery disease and presence of the PlA2 allele was not observed.20 The prevalence of the PlA2 allele was 50% in men having a MI before the age of 47 years.21 A statistical interaction between the PlA2 allele and cholesterol levels, as they combine to affect MI prevalence, has also been noted.12 In a retrospective study of 178 Spanish men <50 years of age, Batalla et al22 found a positive association of the PlA2 allele with high LDL-cholesterol concentrations, but the frequency of the PlA2 allele in subjects with CHD was not different from that of age- and sex- matched control subjects. All of these studies were nonprospective and not population-based and therefore were potentially subject to bias. Even though the stronger association of the PlA2 with coronary artery disease at a younger age7 argues for a pathogenic role of the PlA2 allele, such an age interaction was not observed in several other studies.11 13 23 24 The present prospective study is based on follow-up of a cohort of 15 792 healthy individuals who were selected from 4 communities in the United States. These individuals had been followed since enrollment in 1987 to 1989. Ascertainment of CHD was based on strict, standardized criteria. The frequency of the PlA1/PlA2 plus PlA2/PlA2 genotypes was not significantly different between cases and noncases, indicating a lack of an association between the PlA2 allele and incident CHD. A vast majority of our cases were <60 years of age. Although the number of cases >60 years was too small for statistical analysis, our results are unlikely to show an age interaction with PlA genotypes.
It has been suggested that the relation of the PlA2 polymorphism could differ with different coronary phenotypes: acute coronary syndrome versus coronary atherosclerosis. The inclusion criteria for the CHD events in our study allow enrollment of subjects who had a coronary revascularization procedure. To estimate if the association of the PlA2 polymorphism with CHD incidence will change if cases were restricted to those with a proven acute coronary syndrome, the analysis was repeated after removing silent MI and procedure-related events (30.5% of events removed). It yielded similar results for the subset with acute CHD syndromes, that is, the association remained nonsignificant. No significant relation between established CHD risk factors and the PlA2 allele was noted either. Our results are similar to those reported for the prospective Physician’s Health Study (PHS) cohort, which did not show a statistically significant difference in PlA2 frequency between incident CHD cases and control subjects.23 Notably, the PHS included only men. Observations of our study extend to both men and women and to whites and blacks.
The hypothesis that the PlA2 polymorphism is an important inherited risk factor for CHD implies an increase in platelet activation as a mediator of the thrombotic event. Our study did not find an enhancement of platelet activation in individuals with the PlA2 allele, as measured by plasma ß-TG levels. In another study25 of patients with acute stroke and control subjects, levels of ß-TG and platelet factor 4 were not associated with the PlA2 allele. In the PHS study, aspirin did not provide any more protection to individuals carrying at least 1 copy of the PlA2 allele compared with those with the PlA1/A1 genotype.24 On the other hand, the Framingham Offspring Study5 showed that PlA2 allele was associated with increased platelet aggregability by epinephrine, suggesting that molecular variants of the GPIIIa gene play a role in platelet reactivity in vitro. A higher prevalence of the PlA2 polymorphism has been reported in siblings of patients with premature CHD than in those of a race-matched and geographic area–matched control cohort, who remained asymptomatic.26 The occurrence of a genetic defect that could lead to an increase in CHD may also cluster within families with strong familial aggregation of CHD. However, in a study of 1292 adults from 515 such families, no increased frequency of the PlA2 allele was noted, and earlier onset of CHD prevalence was not influenced by the presence or absence of the PlA2 allele.10 Taken together, the reported data indicate that healthy individuals carrying the PlA2 allele do not have an increased risk of CHD.
Our study has several advantages over the nonprospective case-control studies in that it is population based, prospective in nature, and contains a relatively large number of participants and incident events. A limitation of this study is the inclusion of subjects who were 45 to 64 years of age at entry into the study. If PlA2, like other genetic factors, were to play a more important role in increasing CHD risk in young subjects, we might have missed individuals dying young or having premature CHD who would be excluded from our study. Hence, the interpretation of results from this population-based prospective follow-up study should be applied to middle-aged men and women only.
|
Acknowledgments |
|---|
The ARIC study was funded by National Heart, Lung, and Blood Institute contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, and N01-HC-55022. We appreciate the important contributions of the following ARIC personnel: Debbie Rubin Williams, Patsy H. Tacker, Lily Wang (University of North Carolina Coordinating Center, Chapel Hill); Leslie Angel-Potter, Dawn Scott, Nadine Shelton (University of North Carolina, Chapel Hill); Julia Fleshman, Kathy Joyce, Charlene Kearney-Cah (Wake Forest University, Winston-Salem); Bobbie J. Alliston, Barbara Davis, Agnes Hayes (University of Mississippi Medical Center, Jackson); Maxine Dammen, Caryl DeYoung, Christine Dwight (University of Minnesota, Minneapolis); Sunny Harrell, Patricia Hawbaker, Joan Nelling (Johns Hopkins University, Baltimore); Willa Wang, Christy Moore, Johnna Kincaid, Susan Mitterling, (University of Texas Medical School, Houston); and Wanda R. Alexander, Christie M. Ballantyne, and Val Creswell (Methodist Hospital, Atherosclerosis Clinical Laboratory, Houston).
|
Footnotes |
|---|
Guest Editor for this article was Klaus Lindpaintner, MD, Brigham and Womens Hospital, Boston, Mass.
Received October 7, 1999; revision received May 8, 2000; accepted May 30, 2000.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
-
Wu KK. Platelet activation mechanisms and
markers in arterial thrombosis. J Intern
Med. 1996;239:17–34.[Medline]
[Order article via Infotrieve]
-
Patrono C. Prevention of myocardial infarction and
stroke by aspirin: different mechanisms? Different dosage? Thromb
Res. 1998;92(suppl 1):S7–12.
-
Coller BS, Anderson KM, Weisman HF. The
anti-GPIIb-IIIa agents: fundamental and clinical aspects.
Haemostasis. 1996;26(suppl 4):285–293.
-
Trip MD, Cats VM, vanCapelle FJL, et al. Platelet
hyperreactivity and prognosis in survivors of myocardial infarction.
N Engl J Med. 1990;322:1549–1554.[Abstract]
-
Feng DL, Lindpainter K, Larson MG, et al. Increased
platelet aggregability associated with GPIIIa
PlA2 polymorphism: the Framingham Offspring
Study. Arterioscler Thromb Vasc Biol. 1999;19:1142–1147.
[Abstract/Free Full Text]
-
Ridker PM, Manson JE, Buring JE, et al. Circadian
variation of acute myocardial infarction and the effect of low-dose
aspirin in a randomized trial of physicians. Circulation. 1990;82:897–902.
[Abstract/Free Full Text]
-
Weiss EJ, Bray PF, Tayback M, et al. 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]
-
Wu KK, Aleksic N. Platelet
glycoprotein polymorphism and risk for coronary
heart disease. Blood Coagul Fibrinol. 1999;10(suppl
1):S63–S65.
-
Calvete JJ. Clues for understanding the structure and
function of a prototypic human integrin: the platelet
glycoprotein IIb/IIIa complex. Thromb Haemost. 1994;72:1–15.[Medline]
[Order article via Infotrieve]
-
Garg UC, Arnett DK, Folsom AR, et al. Lack of
association between platelet glycoprotein IIb/IIIa
receptor PlA polymorphism and
coronary artery disease or carotid intima-media thickness.
Thromb Res. 1998;89:85–89.[Medline]
[Order article via Infotrieve]
-
Sperr WR, Huber K, Roden M, et al. Inherited
platelet glycoprotein polymorphisms and a risk for
coronary heart disease in young Central Europeans. Thromb
Res. 1998;90:117–123.[Medline]
[Order article via Infotrieve]
-
Carter AM, Ossei-Gerning N, Wilson IJ, et al.
Association of the platelet PlA
polymorphism of glycoprotein IIb/IIIa and the
fibrinogen Bß 448 polymorphism with myocardial infarction and
extent of coronary artery disease. Circulation. 1997;96:1424–1431.
[Abstract/Free Full Text]
-
Herrmann S-M, Poirier O, Marques-Vidal P, et al.
The Leu33/Pro polymorphism
(PlA1/PlA2) of the
glycoprotein IIIa (GPIIIa) receptor is not related to
myocardial infarction in the ECTIM study. Thromb Haemost. 1997;77:1179–1181.[Medline]
[Order article via Infotrieve]
-
ARIC Investigators. The Atherosclerosis
Risk in Communities (ARIC) study: design and objectives. Am
J Epidemiol. 1989;129:687–702.
[Abstract/Free Full Text]
-
Folsom AR, Wu KK, Rosamond WD, et al. Prospective study
of hemostatic factors and incidence of coronary heart disease:
the Atherosclerosis Risk in Communities (ARIC) study.
Circulation. 1997;96:1102–1108.
[Abstract/Free Full Text]
-
Folsom AR, Nieto FJ, McGovern PG, et al. Prospective
study of coronary heart disease incidence in relation to
fasting, total homocysteine, related genetic polymorphisms, and B
vitamins: the Atherosclerosis Risk in Communities
(ARIC) Study. Circulation. 1998;98:204–210.
[Abstract/Free Full Text]
-
Papp AC, Hatzakis H, Bracey A, et al. ARIC Hemostasis
Study-I: development of blood collection and processing systems
suitable for multicenter hemostatic studies. Thromb Haemost. 1989;61:15–19.[Medline]
[Order article via Infotrieve]
-
Ghaddar HM, Cortes J, Salomaa V, et al. Correlation of
specific platelet activation markers with carotid
arterial wall thickness. Thromb Haemost. 1995;74:943–948.[Medline]
[Order article via Infotrieve]
-
Barlow WE. Robust variance estimation for the
case-cohort design. Biometrics. 1994;50:1064–1072.[Medline]
[Order article via Infotrieve]
-
Durante-Mangoni E, Davies GJ, Ahmed N, et al.
Coronary thrombosis and the platelet
glycoprotein IIIA gene PlA2
polymorphism. Thromb Haemost. 1998;80:218–219.[Medline]
[Order article via Infotrieve]
-
Carter AM, Ossei-Gerning N, Grant PJ. Platelet
glycoprotein IIIa PlA
polymorphism in young men with myocardial infarction.
Lancet. 1996;348:485–486.[Medline]
[Order article via Infotrieve]
-
Batalla A, Cubero GI, Reguero JR, et al. Platelet
PlA polymorphism, myocardial infarction, and
extent of coronary artery disease. Circulation. 1998;98:826–827.
[Free Full Text]
-
Ridker PM, Hennekens CH, Schmitz C, et al.
PlA1/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]
-
Osborn SV, Hampton KK, Smillie D, et al.
Platelet glycoprotein IIIa gene polymorphism and
myocardial infarction. Lancet. 1996;348:1309–1310.[Medline]
[Order article via Infotrieve]
-
Carter AM, Catto AJ, Bamford JM, et al. Platelet GP
IIIa PlA and GP Ib variable number tandem
repeat polymorphisms and markers of platelet activation in
acute stroke. Arterioscler Thromb Vasc Biol. 1998;18:1124–1131.
[Abstract/Free Full Text]
-
Goldschmidt-Clermont PJ, Coleman LD, Pham YM, et
al. Higher prevalence of GPIIIa PLA2 polymorphism in siblings of
patients with premature coronary heart disease. Arch
Pathol Lab Med. 1999;123:1223–1229.[Medline]
[Order article via Infotrieve]
This article has been cited by other articles:
 |
|
 |
|
  S. E. Bojesen, K. Juul, P. Schnohr, A. Tybjaerg-Hansen, and B.o. G. Nordestgaard Platelet glycoprotein IIb/IIIa PlA2/PlA2 homozygosity associated with risk of ischemic cardiovascular disease and myocardial infarction in young men: The Copenhagen City Heart Study J. Am. Coll. Cardiol., August 20, 2003; 42(4): 661 - 667. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. B. Braunstein, D. W. Kershner, P. Bray, G. Gerstenblith, S. P. Schulman, W. S. Post, and R. S. Blumenthal Interaction of Hemostatic Genetics With Hormone Therapy : New Insights To Explain Arterial Thrombosis in Postmenopausal Women Chest, March 1, 2002; 121(3): 906 - 920. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. K. Wu and J. T. Willerson Monitoring Platelet Function in Glycoprotein IIb/IIIa Inhibitor Therapy Circulation, May 29, 2001; 103(21): 2528 - 2530. [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||