Role of five platelet membrane glycoprotein polymorphisms in branch retinal vein occlusion.

To determine whether polymorphisms of platelet surface glycoprotein associated with arterial thrombosis are risk factors for branch retinal vein occlusion. A case-control study in which 69 patients with branch retinal vein occlusion and 147 controls who attended the eye clinic for nonvascular complications participated. DNA was extracted from whole blood and analyzed for genotyping of platelet glycoprotein polymorphisms by polymerase chain reactions and specific restricted enzymes. No relationship was found between the four platelet glycoprotein polymorphisms i.e. GPIa C807T, VNTR and Kozak of glycoprotein Ibalpha, the HPA-1 of glycoprotein IIIa and the occurrence of branch retinal vein occlusion. The HPA-2 polymorphism was found in 18 out 60 (30%) patients with branch retinal vein occlusion in comparison with 27 out 142 (19%) of controls, with an estimated odds ratio of 1.8 (95% confidence interval, 0.91-3.65). The four platelet glycoprotein polymorphisms are not risk factors for branch retinal vein occlusion and therefore it seems unnecessary to screen those patients for it. A larger study is required, however, to determine whether HPA-2 is a novel risk factor for branch retinal vein occlusion.     

Platelet functional implications of glycoprotein Ibalpha polymorphisms in African Americans

The platelet glycoprotein Ibalpha is crucial in the binding of platelets to Von Willebrand Factor within areas of high stress. A single nucleotide polymorphism of GP Ibalpha gives rise to the Ko(a) (HPA-2b) and the -5C Kozak polymorphism. The presence of these polymorphisms has been associated with an increased risk for atherothrombotic disease. The Ko(a) polymorphism has been shown to have a higher prevalence in African Americans compared to American Caucasians. However, very little is known regarding any functional consequences of these platelet polymorphisms in African Americans. We assessed the prevalence of the Ko and -5C Kozak polymorphisms in a population of both African American and American Caucasian patients with and without CAD and determined whether there were platelet functional consequences in both groups. We studied 99 patients of which 22 were African American and 77 were American Caucasian. Aggregations were performed and shear induced platelet plug formation was tested using a platelet function analyzer. The HPA-2b allele was significantly higher in African Americans when compared to Caucasians (P = 0.001). Genotype frequencies of the -5C Kozak polymorphism were not significantly different between the two groups. We found no differences in platelet aggregation in African Americans who were either heterozygous or homozygous for the HPA-2b allele or the -5C Kozak allele when compared to American Caucasians of the same category. We found no significant differences in PFA-100 testing. We conclude from our study that these polymorphisms do not lead to altered platelet function in African Americans.     

Glycoprotein Ib polymorphisms influence platelet plug formation under high shear rates

Platelet polymorphisms (Kozak, VNTR and HPA-2) within glycoprotein (GP)Ib alpha may be associated with an increased risk of arterial thrombosis. However, the functional role of these polymorphisms has not been clarified. Their influence on platelet plug formation under high shear rates was, therefore, examined in 233 healthy individuals. Collagen-adrenaline-induced closure time was shorter in carriers of the C/D versus C/C VNTR allele and in homozygotes with the (-5)T/T versus (-5)C/T Kozak genotype as determined by novel polymerase chain reaction methods. The HPA-2 genotype had no effects, and the density of GPIb alpha molecules was not influenced by GPIb alpha genotypes.     

The Kozak sequence polymorphism of platelet glycoprotein Ibalpha and risk of nonfatal myocardial infarction and nonfatal stroke in young women

Several platelet membrane glycoprotein polymorphisms have been identified as potential risk factors for cardiovascular disease. Recently a nucleotide -5T/C dimorphism in the translation initiation site (Kozak sequence) of the platelet glycoprotein Ibalpha (GPIbalpha) gene was associated with increased platelet surface levels of the GPIb-IX-V receptor complex. The role of this GPIbalpha Kozak sequence polymorphism in the occurrence of arterial thrombotic disease is unknown. We performed genotype analysis of the Kozak sequence polymorphism of GPIbalpha in a population-based study of 18- to 44-year-old women with nonfatal myocardial infarction (MI) (n = 78), nonfatal stroke (n = 106), and 384 demographically similar female control subjects. Analysis of -5T/C genotypes revealed that at least one copy of the C allele was present in 14.1% of MI cases, 23.6% of stroke cases, and 23.7% of controls. The age-adjusted odds ratio for MI in women carrying at least one copy of the C allele was 0.53 (95% confidence interval [CI] 0.27-1.05). The age-adjusted odds ratio for stroke in women carrying at least one copy of the C allele was 0.99 (95% CI 0.59-1.65). Analyses stratified by stroke type (ischemic, hemorrhagic) yielded similar results. In conclusion, young women carrying the C allele of the Kozak sequence polymorphism of GPIbalpha are not at increased risk of MI or stroke. Paradoxically, the C allele may even be associated with a reduced risk of MI in this population. This finding requires further study.     

血小板膜糖蛋白Ⅰa和Ⅰbα基因多态性与脑梗死的相关性研究

目的探讨血小板膜糖蛋白(GP)Ⅰa基因和Ⅰbα基因多态性与脑梗死发生的关系,为缺血性脑卒中的预防及治疗提供理论基础。方法选择经CT或MRI证实的脑梗死患者302例(脑梗死组)和健康体检者196例(对照组);采用PCR-RFLP方法检测GPⅠa C807T基因与Ⅰbα基因HPA-2、Kozak序列多态性在2组中的分布频率。结果脑梗死组GPⅠa C807T等位基因频率明显高于对照组,差异有统计学意义(P0.05);脑梗死组GPⅠbα基因Kozak序列C等位基因频率明显高于对照组差异有统计学意义(25.33% vs 10.20%,P0.05);脑梗死组GPⅠbα基因HPA-2序列等位基因频率、基因型与对照组比较,差异无统计学意义(P0.05)。结论 GⅠbα基因HPA-2序列多态性与脑梗死无相关性;GPⅠa C807T等位基因和Ⅰbα基因Kozak序列多态性可能是脑梗死的遗传危险因素。     

Genetic variability of platelet glycoprotein Ibalpha gene

Platelet membrane glycoprotein (GP) Ibalpha is a critical component of platelet adhesion complex to subendothelium structures following tissue injury or pathological surfaces, such as atherosclerotic plaques. Polymorphisms of the GPIbalpha gene have been associated with a high risk for occlusive vascular disease, and its distribution varies considerably among distinct populations. These polymorphisms comprise the human platelet antigen (HPA)-2 system, the -5C/T dimorphism of the Kozak sequence, and the variable number of tandem 39-bp repeats (VNTR). Here we report the prevalence of the GPIbalpha gene polymorphisms among Brazilians, a highly ethnically diverse population. We analyzed 492 subjects of European, African, or Indigenous origin. It was possible to determine ten distinct haplotypes. The most common ( reverse similar 40%) haplotype was the Kozak-TT/HPA-2aa/VNTR-CC for both Caucasian and African descent. However, among Indigenous, Kozak-TT/HPA-2aa/VNTR-CC and Kozak-TC/HPA-2aa/VNTR-CC were equally present. Although a strong linkage disequilibrium between VNTR and HPA-2 polymorphism had also been observed, here we determined incomplete linkage disequilibrium in 10% of subjects from all ethnic groups. VNTR-E, a rare variant lacking the 39-bp repeat, was identified in two unrelated subjects, and functional platelet studies revealed no abnormalities. The VNTR-A allele, the largest variant containing four copies of the repeats, was not identified in this population. However, homozygosity for the VNTR-A allele (Kozak-TT/HPA-2aa/VNTR-AA) was determined in two distinct species of nonhuman primates. These results suggest a greater complex evolutionary mechanism in the macroglycoprotein region of the GPIbalpha gene and may be useful in the design of gene-disease association studies for vascular disease.     

Allelic and genotypic frequencies of platelet glycoprotein polymorphisms in a Portuguese population

Introduction and objectivesWe studied genotypic and allelic frequencies of polymorphisms that can affect platelet function, namely the Kozak, VNTR and HPA-2 polymorphisms of glycoprotein Ibα, the Pl^A polymorphism of glycoprotein IIIa and the C807T polymorphism of glycoprotein Ia, in a Portuguese population composed of 227 donors.MethodsPCR-RFLP was used to assess the Kozak, HPA-2, Pl^A and C807T polymorphisms. The VNTR polymorphism was discriminated by different weight bands on electrophoresis.ResultsAll genotypic frequencies were in Hardy-Weinberg equilibrium and do not differ from other Caucasian populations. Genotypic frequencies were 68.3%, 26.9% and 4.8% for Pl^A1/A1, Pl^A1/A2 and Pl^A2/A2 genotypes of the Pl^A polymorphism, 79.3%, 20.3% and 0.4% for TT, TC and CC genotypes of the Kozak polymorphism, 81.1%, 18.9% and 0.0% for aa, ab and bb genotypes of the HPA-2 polymorphism, 15.4%, 0.9%, 70.5%, 11.5%, 1.3% and 0.4% for BC, BD, CC, CD, DD and CE genotypes of the VNTR polymorphism, and 39.7%, 50.2% and 10.1% for CC, CT and TT genotypes of the C807T polymorphism.ConclusionsThe Portuguese population has now been characterized in terms of major platelet glycoprotein polymorphisms, which will be an important tool for further studies to assess the role of platelet glycoproteins in individual predisposition to prothrombotic conditions and response to antithrombotic therapy.     

Role of Kozak sequence polymorphism of platelet glycoprotein Ibalpha as a risk factor for coronary artery disease and catheter interventions

OBJECTIVES: We sought to determine the role of the -5T/C polymorphism of the platelet glycoprotein (GP) Ibalpha as a potential risk factor for coronary artery disease (CAD) and adverse events complicating a coronary catheter intervention. BACKGROUND: The platelet GP Ib-IX-V receptor complex plays a crucial role in arterial thrombus formation. The -5T/C polymorphism of GP Ibalpha is associated with increased receptor density. METHODS: We genotyped 1,000 patients with angiographically confirmed CAD, as well as 1,000 age- and gender-matched control subjects, for this polymorphism by polymerase chain reaction/restriction fragment length polymorphism. Among the patients with CAD, 269 underwent percutaneous transluminal coronary angioplasty (PTCA), 103 underwent directional coronary atherectomy and 278 underwent stenting. This intervention group was followed for a 30-day composite end point of target vessel revascularization, myocardial infarction or death. RESULTS: Carriers of the -5C allele were significantly over-represented in the group of patients developing acute coronary syndromes (relative risk [RR] 1.43, 95% confidence interval [CI] 1.05 to 1.95, p = 0.02). The -5C allele furthermore predicted an increased risk for developing complications after PTCA (RR 3.75, 95% CI 1.15 to 12.27, p = 0.029). CONCLUSIONS: The -5C allele of the GP Ibalpha Kozak polymorphism may represent a risk factor in clinical conditions in which thrombosis plays an important role, such as in acute coronary syndromes and in complications after PTCA.     

New alleles of the platelet glycoprotein Ibα gene

Platelet membrane glycoprotein Ibα (GP Ibα) bears two molecular polymorphisms which are in linkage disequilibrium: the C/T dimorphism at codon 145 (HPA-2) and the variable number of tandem repeats (VNTR) polymorphism in the macroglycopeptide region. The frequencies of these two polymorphisms, and of another three recently described silent polymorphisms, were investigated by genotypic identification in 729 Caucasian individuals from the south of Spain. Eight different alleles of this gene, including the longest VNTR A allele of the GP Ibα gene, were found in this population. Moreover, we detected an unexpected linkage between the B and A variants of the VNTR polymorphism and the HPA-2a allele in 5.9% of this population. These results suggest a new evolutionary model of GP Ibα, in which homologous recombination could account for the genetic diversity of the GP Ibα.     

血小板膜糖蛋白Ⅰb Kozak序列-5T/C及纤维蛋白原β-148C/T基因多态性与脑梗死

目的研究雷州半岛地区汉族人群血小板膜糖蛋白(GP)ⅠbKozak序列-5T/C和纤维蛋白原(Fib)β-148C/T基因多态性位点与脑梗死的关系。方法选择雷州半岛地区汉族人群健康体检者130例(对照组)和经头颅CT和(或)MRI证实的脑梗死患者148例(脑梗死组),用PCR-RFLP检测GPⅠbKozak序列-5T/C和Fibβ-148C/T基因多态性,分析两组频率分布特点及与脑梗死的关系。结果脑梗死组β-148C/T位点T等位基因频率为30.1%,对照组为21.9%,(P<0.05),脑梗死组GPⅠbKozak序列C等位基因频率为48.7%,对照组为39.6%,(P<0.05),两个多态性位点连锁不平衡系数D为-0.018(P>0.05)。结论Fibβ-148C/T位点T等位基因和GPⅠbKozak序列C等位基因是雷州半岛地区汉族人群脑梗死的遗传易感因素,但二者不存在连锁不平衡关系。     

Role of 4 platelet membrane glycoprotein polymorphisms on experimental arterial thrombus formation in men.

This study investigates whether the polymorphisms of 3 important platelet receptors affected experimental thrombus formation in men. Forty healthy male volunteers randomly recruited were genotyped for the variable number of tandem repeat (VNTR) of GPIbalpha, the -5T/C polymorphism in the Kozak sequence of GPIbalpha, the 807C/T polymorphism of GPIa, and the PI(A1)/PI(A2) polymorphism of GPIIb/IIIa. Platelet thrombus formation was induced ex vivo by exposing a collagen-coated coverslip in a parallel plate perfusion chamber to native blood for 4 minutes. The shear rates at the collagen surface were 650 and 2600 x s(-1). At 2600 x s(-1) platelet thrombus formation was significantly related only to the 807C/T polymorphism. In contrast, at 650 x s(-1) thrombus formation was significantly altered only by the Kozak sequence polymorphism. The VNTR and the PI(A1)/PI(A2) polymorphisms did not influence thrombus formation. Thus, platelet thrombus formation is significantly influenced by genetic variations of the GPIbalpha and GPIa receptors. The effect of these polymorphisms was dependent on the blood flow rate.     

Resistance in vitro to low-dose aspirin is associated with platelet PlA1 (GP IIIa) polymorphism but not with C807T(GP Ia/IIa) and C-5T Kozak (GP Ibalpha) polymorphisms

OBJECTIVES: We investigated whether three platelet gene polymorphisms, Pl(A1/A2), C807T, and C-5T Kozak (encoding, respectively, for platelet membrane glycoproteins (GP) IIIa, GP Ia/IIa, GP Ibalpha), could contribute to the resistance to a low dose of aspirin (160 mg/day). BACKGROUND: Aspirin antiplatelet effect is not uniform in all patients, and the mechanism by which some patients are in vitro resistant to aspirin remains to be determined. However, it has been suggested that polymorphisms of platelet membrane glycoproteins might contribute to aspirin resistance. METHODS: Ninety-eight patients on aspirin (160 mg/day) for at least one month were enrolled. Aspirin resistance was measured by the platelet function analyzer (PFA)-100 analyzer; genotyping of the three polymorphisms was performed using a polymerase chain reaction-based restriction fragment-length polymorphism analysis. RESULTS: Using a collagen/epinephrine-coated cartridge on the PFA-100, the prevalence of aspirin resistance was 29.6% (n = 29). Aspirin-resistant patients were significantly more often Pl(A1/A1) (86.2%; n = 25) than sensitive patients (59.4%; n = 41; p = 0.01). Of the 29 patients, 25 were reevaluated after having taken 300 mg/day aspirin for at least one month. Only 11 patients still have nonprolonged collagen epinephrine closure time, and these were all Pl(A1/A1). No relation was found between resistance status and C-5T Kozak or C807T genotypes. CONCLUSIONS: Platelets homozygous for the Pl(A1) allele appear to be less sensitive to inhibitory action of low-dose aspirin. This differential sensitivity to aspirin may have potential clinical implications whereby specific antiplatelet therapy may be best tailored according to the patient's Pl(A) genotype.     

脑梗死患者血小板膜糖蛋白Ⅰ bα基因HPA-2、Kozak位点多态性分析

目的观察脑梗死患者血小板膜糖蛋白（GP）Ⅰbα基因HPA-2、Kozak位点多态性,探讨其与脑梗死的关系。方法选取316例经CT或MR I证实的脑梗塞患者（观察组）及209例无脑血管疾病者（对照组）,采用聚合酶链反应—限制性片断长度多态性（PCR-RFLP）法检测GPⅠbα基因HPA-2、Kozak位点多态性,用流式细胞术（FCM）测定血小板活化标志物CD62P、CD63的表达。结果观察组血小板GPⅠbα基因HPA-2位点基因型分布及等位基因频率与对照组相比P均〉0.05;观察组Kozak位点观察组基因型为CC者20例、CT者113例、TT者169例,等位基因C频率为25.33%、T频率为74.67%;对照组分别为6、28、162例和10.20%、89.80%。两组基因型分布和等位基因C、T频率相比,P均〈0.05。观察组表达等位基因C者（基因型CC＋CT）CD62P表达量为20.94±7.35、CD63表达量为28.62±9.47,不表达等位基因C者（基因型为TT）分别为13.36±6.27、20.27±5.45,二者CD62P、CD63表达量相比P均〈0.05。结论 脑梗死患者血小板GPⅠbα基因Kozak位点存在多态性,HPA-2位点未发现多态性。GPⅠbα基因Kozak位点多态性可能通过影响血小板的活化参与脑梗死的发生过程。     

Prothrombotic gene polymorphisms and plasma factors in young north Indian survivors of acute myocardial infarction

The aim of this study was to evaluate the association of prothrombotic gene polymorphisms [factor V Leiden (FVL) 1691GA, factor VII (FVII) 10976GA, FVII HVR4, platelet membrane glycoproteins GP1BA 1018CT, GP1BA VNTR, integrin ITGB3 1565TC, integrin ITGA2 807CT and methylenetetrahydrofolate reductase (MTHFR) 677C/T], plasma factors (fibrinogen and homocysteine) and traditional risk factors with acute myocardial infarction (AMI) in 184 patients ≤ 40 years of age and 350 controls (≤ 40 years) from north India. Multiple logistic-regression analysis showed that hypertension (OR 1.9, 95 % CI 1.1-3.8, p = 0.042), diabetes mellitus (OR 10.5, 95 % CI 2.0-56.7, p = 0.006), smoking (OR 7.1, 95 % CI 3.7-13.6, p < 0.001), low socio-economic status (OR 13.5, 95 % CI 2.3-78.4, p = 0.004), high waist-hip ratio (OR 35.6, 95 % CI 11.1-53.7, p < 0.001) and FVL 1691GA (OR 6.0, 95 % CI 1.2-13.4, p = 0.03) were independent risk predictors of AMI in young. Elevated plasma fibrinogen also showed association with increased AMI risk. ITGA2 807C/T polymorphism showed protection against AMI in univariate analysis only, while GP1BA VNTR-ac (OR 0.4, 95 % CI 0.2-0.9, p = 0.033) showed significant protection even after adjusting for age and sex. Multinominal logistic-regression analysis showed gene-gene (GP1BA 1018C/T with GP1BA VNTR and ITGA2 807C/T with ITGB3 1565T/C polymorphisms) and gene-environment interactions (gene polymorphisms with smoking) operating in the occurrence of AMI in young. In conclusion, the role of inherited predisposition to thrombosis in complex, polygenic and multifactorial disease like AMI is limited to certain genetic factors, in combination with environmental factor like smoking.     

Polymorphism of the human platelet antigen-5 system is a risk factor for occlusive vascular complications in patients with sickle cell anemia

BACKGROUND: Polymorphisms of platelet membrane glycoproteins such as human platelet antigen (HPA)-1b, HPA-2b, the -5T/C Kozak sequence and C807T have been described as risk factors for vascular disease. Vaso-occlusion episodes are a common feature of sickle cell anaemia (SCA), leading to complications such as stroke, acute chest syndrome, avascular head femur necrosis and priapism. Complex interactions are involved in vaso-occlusion, and activated platelets may play an important role. These data raised the question of whether platelet polymorphisms could be implicated in occlusive vascular complications (OVC) of SCA. MATERIALS AND METHODS: In this study, 97 patients with SCA were analysed in two groups: 34 patients presenting with OVC (SCA-VC) and 63 without these complications (SCA-N). The distribution of the HPA-1, -2 and -5 systems, as well as C807T dimorphism and -5T/C Kozak sequence alleles, was evaluated using DNA-based methods. RESULTS: Patients of the SCA-VC group showed a higher frequency of the HPA-5b allele (0.324) compared with those of the SCA-N group (0.111) (chi2 = 13.19, P = 0.0002). None of the other polymorphisms, isolated or associated as haplotypes, demonstrated any correlation with the development of OVC in these patients. CONCLUSIONS: The findings of this study suggest that the HPA-5b allele is a genetic risk factor for the development of OVC in patients with SCA. This allele could be explored as a target for the development of new therapeutic approaches.     

Association of platelet collagen receptor polymorphisms with premature acute myocardial infarction

The impact of platelet collagen receptor polymorphisms in the pathogenesis of myocardial infarction at young age remains unknown. To determine whether either of the two platelet collagen receptor polymorphisms (GP VI T13254C and GP Ia C807T) was associated with premature acute myocardial infarction. One hundred patients with premature acute myocardial infarction and 100 age-matched controls with normal coronary angiograms were studied. Genotyping was done using PCR followed by restriction fragment length polymorphism (RFLP). GP Ia C807T polymorphism was more frequent in the patient group (65%) than in the control group (53%). However, there was no association between this polymorphism and premature acute myocardial infarction (P?=?0.08). The prevalence of T13254C polymorphism did not differ between patients (38%) and controls (33%), and this polymorphism was not associated with premature acute myocardial infarction (P?=?0.46). Logistic regression analysis also indicated no association between these polymorphisms and premature acute myocardial infarction (C807T with P?=?0.51 and T13254C with P?=?0.20). There is no association between GP VI T13254C or GP Ia C807T polymorphisms and premature acute myocardial infarction.     

Requirement of leucine-rich repeats of glycoprotein (GP) Ibalpha for shear-dependent and static binding of von Willebrand factor to the platelet membrane GP Ib-IX-V complex

The platelet glycoprotein (GP) Ib-IX-V complex mediates adhesion to von Willebrand factor (vWf) in (patho)physiologic thrombus formation. The vWf-binding site on GP Ib-IX-V is within the N-terminal 282 residues of GP Ibalpha, which consist of an N-terminal flanking sequence (His-1-Ile-35), 7 leucine-rich repeats (Leu-36-Ala-200), a C-terminal flank (Phe-201-Gly-268), and a sulfated tyrosine sequence (Asp-269-Glu-282). We have used mammalian cell expression of canine-human chimeras of GP Ibalpha, corresponding to precise structural boundaries, to demonstrate the first specific requirement for individual leucine-rich repeats for binding of vWf either induced by a modulator, ristocetin, or under hydrodynamic flow. Implicit in this approach was that the GP Ibalpha chimeras retained a functional conformation, a supposition confirmed by analyzing restoration of function to reversed human-canine chimeras and demonstrating that all chimeras bound vWf activated by botrocetin, a modulator that is indiscriminate between species. Leucine-rich repeats 2, 3, and 4 of GP Ibalpha were identified as being critical for vWf adhesion to GP Ib-IX-V.     

Polymorphisms of platelet membrane glycoprotein Ib alpha and plasma von Willebrand factor antigen in coronary artery disease.

To examine the relationships of two polymorphisms of platelet glycoprotein (GP) Ib alpha and coronary artery diseases (CAD) in Japanese patients, we conducted a case-control study with 158 Japanese patients and 169 control subjects. The frequencies of HPA-2 polymorphism and the variable number of tandem repeat (VNTR) polymorphisms in the macroglycopeptide region did not significantly differ between CAD patients and control subjects. The polymorphisms of GPIb alpha were not associated with the number of affected vessels in CAD patients. When patients with acute coronary syndrome only were analyzed, the frequencies of the two polymorphisms of GPIb alpha showed no significant difference. Although plasma von Willebrand antigen (vWF:Ag) levels in patients were significantly higher than in controls, no association between vWF concentration and GPIb genotypes was observed. In patient groups with higher or lower vWF:Ag concentrations, no increase in the frequencies of Met145 or larger VNTR polymorphisms was seen in either group. Our findings indicate that no association exists between the frequencies of the two polymorphisms of GPIb alpha and CAD.     

Platelet receptor HPA-1 polymorphism of alphaIIbbeta3 and 807 C/T polymorphism of alpha2beta1 and Buerger's disease

Thromboangiitis obliterans or Buerger's disease is an episodic and segmental inflammatory and thrombotic process of the medium and small arteries of the lower extremities. Even though the disease was described 90 years ago, the etiopathogenesis is still under consideration. Afflicted patients are mostly young male cigarette smokers without signs of atherosclerosis or other risk factors for peripheral arterial occlusive disease. This indicates that hereditary thrombophilic factors could play a role in the etiopathogenesis. Recently, increasing evidence shows that platelet receptor polymorphisms (HPA-1 polymorphism of beta3 subunit of alphaIIbbeta3 and 807 C/T polymorphism alpha2beta1) are associated with early onset of arterial thrombosis (myocardial infarction, stroke). This case-control study was designed to assess whether the 807 C/T polymorphism or the HPA-1 polymorphism is involved in the pathogenesis of Buerger's disease or has any influence on the clinical course of Buerger's disease. Eighteen patients with Buerger's disease and 81 (sex and age matched) healthy control subjects (mean age 44 +/- 10 vs 45 +/- 8 years, respectively) were genotyped for platelet receptor HPA-1 and GPIa 807 C/T polymorphism. The gene frequency of HPA-1 and GPIa 807 C/T polymorphisms was identical in both groups. Prevalence of hetero- and homozygous carriers of the HPA-1b allel (1a1b and 1b1b genotype) as well as the prevalence of the 807 C/T and 807 T/T carriers did not differ significantly between the two groups, p >0.05. The grade of clinical disease manifestation as well as disease progression did not reveal any significant relationship with HPA-1 and 807 C/T polymorphisms. A relationship between the age at onset of the disease and HPA-1 polymorphism was not found. Otherwise analysis of the GPIa 807 C/T platelet receptor polymorphism showed that the average age of patients who are carriers of the T allele at early onset of disease was 32 +/- 6 years (range 27-48 years) compared to 42 +/- 6 years (range 34-53 years) of the C/C carriers (p <0.05). This indicates that the GPIa 807 C/T polymorphism does not represent a risk factor for Buerger's disease itself, but could be associated with premature onset of this disorder in predisposed individuals.