The PlA1/A2 Polymorphism of Glycoprotein IIIa as a Risk Factor for Stroke: A Systematic Review and Meta-Analysis

Floyd, Christopher N.; Ellis, Benjamin H.; Ferro, Albert

doi:10.1371/journal.pone.0100239

Cited by 33 publications

(41 citation statements)

References 72 publications

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“…It was shown by Floyd et al 27 that an expression of the PlA2 allele of glycoprotein IIIa has an impact on platelet function. In this work, we studied the platelet nanomechanics and compared the topology and Young's modulus of platelets derived from healthy individuals and patients with DVT who either carry or not PlA2 allele in GPIIb/IIIa gene.…”

Section: Discussionmentioning

confidence: 99%

“…23 The carriage of PlA2 allele has been associated with an increased risk of myocardial infarction and stroke and was postulated as a risk factor for venous thromboembolism (VTE). [24][25][26][27][28] Platelets play an important role in the development of venous thrombosis, and along with slow blood flow and vein wall damage, they contribute to a hypercoagulable and prothrombotic state. The occurrence of multiple interacting risk factors is a precondition for VTE development.…”

Section: Introductionmentioning

confidence: 99%

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PlA2 Polymorphism in Glycoprotein IIb/IIIa Modulates the Morphology and Nanomechanics of Platelets

Todinova

Komsa-Penkova

Krumova

et al. 2017

Clin Appl Thromb Hemost

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Glycoprotein IIb/IIIa (GPIIb/IIIa) is the most abundant platelet surface receptor for fibrinogen and von Willebrand factor. Polymorphism PlA1/A2 in the gene of GPIIb/IIIa is among the risk factors for the development of arterial and venous thrombosis. The aim of this study is to evaluate the effect of the carriage of PlA1/A2 on the size, topographic features, and membrane stiffness of platelets from healthy controls and patients with deep venous thrombosis (DVT). Atomic force microscopy (AFM) imaging and nanoindentation (force-distance curves) were applied to investigate the morphological and nanomechanical properties (Young's modulus) of platelets immobilized on glass surface. The surface roughness (R a ) and height (h) of platelets from patients with DVT, carriers of mutant allele PlA2 (R a ¼ 30.2 + 6 nm; h ¼ 766 + 182 nm) and noncarriers (R a ¼ 28.6 + 6 nm; h ¼ 865 + 290 nm), were lower than those of healthy carriers of allele PlA2 (R a ¼ 48.1 + 12 nm; h ¼ 1072 + 338 nm) and healthy noncarriers (R a ¼ 49.7 + 14 nm; h ¼ 1021 + 433 nm), respectively. Platelets isolated from patients with DVT, both carriers and noncarriers, exhibit much higher degree of stiffness at the stage of spreading (E ¼ 327 + 85 kPa and 341 + 102 kPa, respectively) compared to healthy noncarriers (E ¼ 198 + 50 kPa). In addition, more pronounced level of platelet activation was found in polymorphism carriers. In conclusion, the carriage of PlA2 allele modulates the activation state, morphology, and membrane elasticity of platelets.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

PlA2 Polymorphism in Glycoprotein IIb/IIIa Modulates the Morphology and Nanomechanics of Platelets

Todinova

Komsa-Penkova

Krumova

et al. 2017

Clin Appl Thromb Hemost

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“…Since the study of Weiss et al is the first study which has reported P1A2 polymorphism as a risk factor for MI, some studies in the literature have been shown inconsistent results. 9,13,21,22 Several studies demonstrated that the P1A2 polymorphism is a strongly associated with MI. [23][24][25] Rest of studies did not find any results to verify this relationship.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to this, a recent meta-analysis study has shown the significant relationship between increased MI risk and PlA2 polymorphism risk under 45 years old male patients. 13 Individuals that have PlA2 allele eventually have overly active thrombin in their blood and shown to have increased levels of coagulations after microvascular injury in muscle tissue.…”

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confidence: 99%

The Relation Between the P1A1/A2 Polymorphism of ITGB3 Gene and Myocardial Infarction in Elite Athletes

Günel¹,

Antal²,

Senturk³

et al. 2017

Turkiye Klinikleri J Med Sci

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A AB BS S T TR RA AC CT T O Ob bj je ec ct ti iv ve es s: : P1A1/A2 polymorphism on Integrin Subunit Beta 3 (ITGB3) gene's correlation with increased risk of myocardial infarction (MI) is not clear and various researches have reported contradictory results concerning the P1A1/A2 polymorphism of ITGB3 gene. We have focused on the relation P1A1/A2 polymorphism and MI, 26 male subjects under 45 years old who had MI. Due to the increasing concern of sudden death on athletes, we have compared these subjects with professional athletes. We aimed to investigate the frequency of P1A1/A2 polymorphism, in subjects under 45 years old suffering myocardial infarction (MI) and elite athletes who are at the same age range. M Ma at te er ri ia al l a an nd d M Me et th ho od ds s: : Peripheral blood was collected from 26 subjects with MI grouped as positive control, 25 healthy subjects grouped as negative control and 37 subjects as elite athletes. DNA was isolated from totally 88 peripheral blood samples. DNA extraction was followed by the PCR-RFLP method in order to detect the PlA1/A2 polymorphism. Amplified DNA products were digested with HpaII restriction enzyme. We aimed to see two bands, at 81 and 127 bp, after enzyme digestion. Standard descriptive statistical methods were applied to summarize the data. R Re e--s su ul lt ts s: : Three genotypes could be determined after assessment with bioanalyzer; genotype P1A1/P1A1 (81 and 127 bp fragments), genotype P1A1/P1A2 (81,127 and 208 bp fragments) and genotype P1A2/P1A2 (208 bp). Heterozygous polymorphic phenotype (P1A1/P1A2) was observed 8%, 7.7% and 17% on positive control group, negative control group, and elite athletes, respectively. Homozygous phenotype (PlA2/A2) was observed in 7.7% of positive control group only. C Co on nc cl lu us si io on n: : Our study highlights the significance of screening on athletes to prevent sudden deaths during sports. For next step, these obtained results will be analysed on larger populations to try to answer the question that "can sudden cardiac deaths (SCDs) be avoided and what should be done?" K Ke ey yw wo or rd ds s: : Myocardial infarction; polymorphism, genetic; ITGB3 protein, human Ö ÖZ ZE ET T A Am ma aç çl la ar r: : İntegrin Subünit Beta 3 (ITGB3) genindeki P1A1/A2 polimorfizmi ile miyokard infarktüsü (MI) artan riski ile ilişkisi net değildir ve çeşitli araştırmalar ITGB3 geninin P1A1/A2 polimorfizmi ile ilgili çelişkili sonuçlar bildirmiştir. P1A1/A2 polimorfizm ve MI arasındaki ilişkiye, 45 yaşın altındaki 26 erkek MI hastası üzerinde odaklandık. Atletlerde ani ölümle ilgili artan endişeler nedeniyle, bu örnekleri profesyonel sporcularla karşılaştırdık. Kırk beş yaş altı miyokard infarktüsü (MI) geçirmiş bireylerde ve aynı yaş aralığında elit atletlerde P1A1/ A2 polimorfizm sıklığını araştır-mayı amaçladık. G Ge er re eç ç v ve e Y Yö ön nt te em ml le er r: : Pozitif kontrol grubu olarak MI hastası 26 örnekten, negatif kontrol olarak gruplandırılan 25 sağlıklı örnekten ve elit atlet grubu olarak 37 örnekten periferik kan top...

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“…Clinical pregnancy rate was approximately 17 % higher for the Gpllla-PIA1 homozygotes than that in the Gpllla-PIA2 carriers (56 versus 48 %, p = 0.010). This correlation probably has not been able to reach strict statistical significance due to the use of an unselected group of participants undergoing their first IVF cycle, despite their large number, and the simultaneous comparison of nine SNPs which decreased the power of the study due to the necessary Bonferroni correction.The Gpllla-PIA2 allele constitutes a significant risk factor for arterial thrombosis [7,8], and more recent studies show that probably it is positively associated with deep venous thrombosis, as well [9]. In a recent pilot study of 60 strictly selected women with unexplained recurrent IVF-ET failures excluding all cases with other known risk factors, we reported an increased occurrence of carriers of the Gpllla-PIA2 allele, Capsule In contrast to the inconclusive results yielded for most inherited thrombophilic factors, there is accumulating evidence that the PIA2 allele of the platelet glycoprotein IIIa gene is associated with increased risk of IVF implantation failure.…”

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confidence: 99%

The PlA2 variant of the platelet glycoprotein IIIa as a genetic risk factor for IVF implantation failure: accumulating evidence

Vlachadis

Vrachnis

Economou

2016

J Assist Reprod Genet

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We read with great interest the recent article of Patounakis et al. [1] who examined the potential role of nine genetic thrombophilic factors in in vitro fertilization (IVF) outcome. Even though the authors came to the conclusion that the thrombophilic single nucleotide polymorphisms (SNPs) which were evaluated, individually or cumulatively, do not have any significant effect, an important clinical finding, the correlation of the genetic polymorphism PIA1/PIA2 (T1565C-Leu33Pro) (rs5918) of the platelet glycoprotein llla (Gpllla) gene with implantation failure after IVF embryotransfer (IVF-ET failure), was overlooked.Expanding the findings of many studies concerning miscarriages, a number of researchers reported that thrombophilic factors affect the success of implantation or the accomplishment of clinical pregnancy in IVF treatment. A large majority of these studies examined the role of anti-phospholipid antibodies in the IVF outcome, and Di Nisio et al. [2] in their meta-analysis of 20 case-control studies including 3542 patients calculated a 3.3-fold increased risk, although this was not confirmed in the respective analysis of cohort studies. On the contrary, since the first published study by Grandone et al. [3] which found that the prevalence of the factor V Leiden (FVL) and prothrombin 20210A allele carriers cumulatively was significantly higher in a small group of 18 women with ≥3 IVF-ET failures (implantation failures or fetal loss), as compared with 216 fertile women with uneventful pregnancies after spontaneous conception, a small number of relative studies that followed have not given conclusive results while certain correlations of genetic thrombophilic factors with IVF-ET failure have ensued with an additive nonspecial approach. Moreover, from the genetic variants that are relative to the coagulation factor gain of function (factors I, II, V, XII), anticoagulant deficiency (plasminogen activator inhibitor-1, PAI-1) or hyperhomocysteinemia (methylene tetrahydrofolate reductase, MTHFR) which were assessed in the study of Patounakis et al., only FVL [4, 5] and MTHFR-677TT [4, 5] and MTHFR-1298CC [6] homozygosities have been singly associated with a negative IVF outcome so far, while noncorrelation was also found in the meta-analysis of Di Nisio et al. with the exception of FVL [2].We consider that the most significant finding of the study of Patounakis et al. is the indication of additional suggestive evidence (although non-significant under strict statistical consideration) that the presence of the GpIIIa-PIA2 allele increases the risk of IVF-ET failure. Clinical pregnancy rate was approximately 17 % higher for the Gpllla-PIA1 homozygotes than that in the Gpllla-PIA2 carriers (56 versus 48 %, p = 0.010). This correlation probably has not been able to reach strict statistical significance due to the use of an unselected group of participants undergoing their first IVF cycle, despite their large number, and the simultaneous comparison of nine SNPs which decreased the power of the study due to the necessa...

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The PlA1/A2 Polymorphism of Glycoprotein IIIa as a Risk Factor for Stroke: A Systematic Review and Meta-Analysis

Cited by 33 publications

References 72 publications

PlA2 Polymorphism in Glycoprotein IIb/IIIa Modulates the Morphology and Nanomechanics of Platelets

PlA2 Polymorphism in Glycoprotein IIb/IIIa Modulates the Morphology and Nanomechanics of Platelets

The Relation Between the P1A1/A2 Polymorphism of ITGB3 Gene and Myocardial Infarction in Elite Athletes

The PlA2 variant of the platelet glycoprotein IIIa as a genetic risk factor for IVF implantation failure: accumulating evidence

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