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Allelic and genotypic frequencies of platelet glycoprotein polymorphisms in a Portuguese population
Frequências alélicas e genotípicas de polimorfismos das glicoproteínas plaquetárias numa população portuguesa
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Most platelet receptors are protein complexes with two or more polypeptide subunits in the platelet membrane. Interindividual differences in platelet responsiveness are usually found, and thus it is reasonable to suggest that in certain circumstances inherited variations in platelet glycoproteins (GP) may contribute to their functional heterogeneity. In fact, three major platelet membrane adhesion receptors – the GPIb-IX-V complex, integrin α2β1 (GPIa-IIa) and integrin α2bβ3 (GPIIb-IIIa) – present genetic polymorphisms that can affect platelet responsiveness.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–6</span></a> Identification of such polymorphisms may thus be useful to assess disease predisposition and response to therapy.</p><p id="par0010" class="elsevierStylePara elsevierViewall">The GPIb-IX-V complex mediates the initial adhesion of platelets to the subendothelial matrix under high shear stress conditions, via von Willebrand factor (vWF) binding.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> The GPIb subunit is composed of two disulfide-linked polypeptides, GPIbα and GPIbβ. GPIbα, the largest protein of the complex, contains the binding sites for vWF and α-thrombin, both platelet activator ligands.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> At least three previously described polymorphisms may influence the function and expression of the GPIbα subunit: a molecular weight polymorphism due to a variable number of tandem repeats (VNTR) within the mucin-like macroglycopeptide region of GPIbα,<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> a threonine-to-methionine substitution at amino acid 145 that forms the basis of the HPA-2 platelet alloantigen system,<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> and a polymorphic variation at position -5 from the ATG start codon, where either T or C is present, called the Kozak polymorphism.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Integrin α2β1, also called the GPIa-IIa complex, is a major collagen receptor in platelets and other cell types. GPIa-IIa mediates platelet adhesion to collagen after an initial subendothelial interaction mediated by GPIb-IX-V and vWF.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> The T allele of the C807T polymorphism within the coding region of the GPIa gene (<span class="elsevierStyleItalic">ITGA2</span>) has been associated with high expression of the receptor and with possible platelet hyperreactivity, even though this polymorphism does not alter amino acids.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,5</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The β3 integrin subunit (GPIIIa) plays a pivotal role in platelet aggregation. The β3 subunit forms a heterodimeric complex with the α2b integrin subunit (GPIIb). The major ligands for this glycoprotein are fibrinogen and vWF, when they are immobilized or in circulation after platelet activation.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> There are at least nine GPIIIa polymorphisms,<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> incompatibility for the HPA-1 (Pl<span class="elsevierStyleSup">A</span>) alloantigens being the most common cause of fetal and neonatal alloimmune thrombocytopenia in Caucasians.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Studies on the functional consequences of this polymorphism in thrombotic diseases have yielded conflicting results,<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12,13</span></a> but an increase in platelet reactivity has been reported in Pl (A2) carriers compared with Pl (A1/A1) individuals.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">In view of the importance of genetic variants in platelet function and the controversy surrounding the clinical correlation between them and prothrombotic conditions, further studies appear to be required in specific populations, that will lead to a better understanding of molecular markers with important roles in platelet function. Since there are no data regarding platelet polymorphism frequencies in the Portuguese population, the aim of this study is to assess allelic and genotypic frequencies of polymorphisms that can affect platelet function, namely the Kozak, VNTR and HPA-2 polymorphisms of the <span class="elsevierStyleItalic">GP1BA</span> gene (GPIbα), the Pl<span class="elsevierStyleSup">A</span> polymorphism of the <span class="elsevierStyleItalic">ITGB3</span> gene (GPIIIa), and the C807T polymorphism of the <span class="elsevierStyleItalic">ITGA2</span> gene (GPIa) in a normal Portuguese population.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Population</span><p id="par0030" class="elsevierStylePara elsevierViewall">The study population consisted of 227 donors (56 male and 171 female) with ages ranging from 15 to 69 years (mean 27 years). This sample is part of a university population (students and employees) in which the majority of students are female. At the time of the sample collection donors had no clinical signs of any hemorrhagic or thrombotic disease. Clinical data regarding blood pressure, presence of diabetes, body mass index, smoking status, physical exercise and family history of cardiovascular disorders were collected but were not used to exclude any donor. Every donor was born in Portuguese territory, as were their parents. All donors gave written informed consent to the protocol, which was approved by the local ethics committee.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Genotype analysis</span><p id="par0035" class="elsevierStylePara elsevierViewall">Genomic DNA was extracted from peripheral blood cells collected by venipuncture in EDTA tubes using a PureLink™ Genomic DNA Mini Kit from Invitrogen. A region containing each polymorphism was amplified by PCR using 1 μg of DNA and 1 μM of specific primers (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). Except for the VNTR polymorphism, amplicons were then digested with specific restriction enzymes (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>) and the digested fragments were visualized in a 2% ethidium bromide agarose gel.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Statistical analysis</span><p id="par0040" class="elsevierStylePara elsevierViewall">Genotypic and allelic frequencies were calculated and Hardy-Weinberg equilibrium was tested for the five polymorphisms by means of a chi-square test using observed vs. expected genotypic frequencies for a significance level of 0.05.</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Results</span><p id="par0045" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows the allelic and genotypic frequencies obtained in the Portuguese population for the five polymorphisms. No major differences were observed compared with results from other Caucasian populations.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> Concerning GPIbα, no bb genotype for the HPA-2 polymorphism or A allele for VNTR were found. The A allele has been described mainly in Japanese and Native American populations.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> Our population is in Hardy-Weinberg equilibrium for the five polymorphisms.</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discussion</span><p id="par0050" class="elsevierStylePara elsevierViewall">There were no available data regarding the allelic frequencies of platelet glycoprotein polymorphisms in the Portuguese population. All these polymorphisms can affect platelet function. GPIIb-IIIa is the most frequent glycoprotein in the platelet surface membrane and the Leu33Pro substitution (Pl<span class="elsevierStyleSup">A</span> polymorphism) is located in the PSI (plexin-semaphorin-integrin) domain, which is known to bind proteins and participate in integrin activation.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> The HPA-2 polymorphism of GPIbα is near the binding site for vWF,<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> VNTR affects GPIbα molecular size<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> and Kozak is near the start codon, which could influence the expression rate of the gene.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> The T allele of the C807T polymorphism of GPIa has also been associated with a higher expression of this glycoprotein on the platelet surface.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Platelet membrane glycoproteins, as key elements for normal primary hemostasis, have also been associated with platelet hyperreactivity and thrombotic mechanisms. A number of clinical studies have reported conflicting data on the association of platelet polymorphisms and increased tendency for thrombosis, and differences between populations may contribute to the contradictory results.<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18–20</span></a> The Portuguese population has now been characterized in terms of major platelet glycoprotein polymorphisms. Our results are of interest in future studies that aim to assess the role of platelet glycoproteins as genetic markers involved in individual predisposition to prothrombotic conditions and in patient response to therapy.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Ethical disclosures</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Confidentiality of data</span><p id="par0060" class="elsevierStylePara elsevierViewall">The authors declare that they have followed the protocols of their work center on the publication of patient data and that all the patients included in the study received sufficient information and gave their written informed consent to participate in the study.</p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflicts of interest</span><p id="par0065" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:2 [ "identificador" => "xres177666" "titulo" => array:5 [ 0 => "Abstract" 1 => "Introduction and objectives" 2 => "Methods" 3 => "Results" 4 => "Conclusions" ] ] 1 => array:2 [ "identificador" => "xpalclavsec166321" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres177667" "titulo" => array:5 [ 0 => "Resumo" 1 => "Introdução e objetivos" 2 => "Métodos" 3 => "Resultados" 4 => "Conclusões" ] ] 3 => array:2 [ "identificador" => "xpalclavsec166320" "titulo" => "Palavras-chave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Population" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Genotype analysis" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Statistical analysis" ] ] ] 6 => array:2 [ "identificador" => "sec0030" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0035" "titulo" => "Discussion" ] 8 => array:3 [ "identificador" => "sec0040" "titulo" => "Ethical disclosures" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0045" "titulo" => "Confidentiality of data" ] ] ] 9 => array:2 [ "identificador" => "sec0050" "titulo" => "Conflicts of interest" ] 10 => array:2 [ "identificador" => "xack45569" "titulo" => "Acknowledgements" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2012-01-12" "fechaAceptado" => "2012-08-02" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec166321" "palabras" => array:4 [ 0 => "Platelet glycoprotein polymorphisms" 1 => "Glycoprotein Ib-IX-V" 2 => "Glycoprotein Ia-IIa" 3 => "Glycoprotein IIb-IIIa" ] ] ] "pt" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palavras-chave" "identificador" => "xpalclavsec166320" "palabras" => array:4 [ 0 => "Polimorfismos das glicoproteínas plaquetárias" 1 => "Glicoproteína Ib-IX-V" 2 => "Glicoproteína Ia-IIa" 3 => "Glicoproteína IIb-IIIa" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span class="elsevierStyleSectionTitle">Introduction and objectives</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">We 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<span class="elsevierStyleSup">A</span> polymorphism of glycoprotein IIIa and the C807T polymorphism of glycoprotein Ia, in a Portuguese population composed of 227 donors.</p> <span class="elsevierStyleSectionTitle">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">PCR-RFLP was used to assess the Kozak, HPA-2, Pl<span class="elsevierStyleSup">A</span> and C807T polymorphisms. The VNTR polymorphism was discriminated by different weight bands on electrophoresis.</p> <span class="elsevierStyleSectionTitle">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">All 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<span class="elsevierStyleSup">A1/A1</span>, Pl<span class="elsevierStyleSup">A1/A2</span> and Pl<span class="elsevierStyleSup">A2/A2</span> genotypes of the Pl<span class="elsevierStyleSup">A</span> 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.</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The 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.</p>" ] "pt" => array:2 [ "titulo" => "Resumo" "resumen" => "<span class="elsevierStyleSectionTitle">Introdução e objetivos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Neste estudo determinámos as frequências alélicas e genotípicas de 5 polimorfismos que poderão afetar a funcionalidade plaquetária, nomeadamente os polimorfismos Kozak, VNTR e HPA-2 da glicoproteína Ibα, o polimorfismo Pl<span class="elsevierStyleSup">A</span> da glicoproteína IIIa e o polimorfismo C807T da glicoproteína Ia numa população portuguesa constituída por 227 dadores voluntários.</p> <span class="elsevierStyleSectionTitle">Métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">A técnica de PCR-RFLP foi usada para determinar os polimorfismos Kozak, HPA-2, Pl<span class="elsevierStyleSup">A</span> e C807T. O polimorfismo VNTR foi discriminado através do padrão eletroforético criado por bandas de peso molecular diferente.</p> <span class="elsevierStyleSectionTitle">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">As frequências genotípicas encontram-se dentro do equilíbrio de Hardy-Weinberg e não diferem estatisticamente de outras populações caucasianas. As frequências genotípicas encontradas foram 68,3, 26,9 e 4,8% para os genótipos Pl<span class="elsevierStyleSup">A1/A1</span>, Pl<span class="elsevierStyleSup">A1/A2</span> e Pl<span class="elsevierStyleSup">A2/A2</span> do polimorfismo Pl<span class="elsevierStyleSup">A</span>, 79,3, 20,3 e 0,4% para os genótipos TT, TC e CC do polimorfismo Kozak, 81,1, 18,9 e 0,0% para os genótipos aa, ab e bb do polimorfismo HPA-2, 15,4, 0,9, 70,5, 11,5, 1,3 e 0,4% para os genótipos BC, BD, CC, CD, DD e CE do polimorfismo VNTR, e 39,7, 50,2 e 10,1% para os genótipos CC, CT e TT do polimorfismo C807T.</p> <span class="elsevierStyleSectionTitle">Conclusões</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">A população portuguesa encontra-se, assim, caracterizada no que respeita aos polimorfismos das principais glicoproteínas plaquetárias, o que poderá servir como ferramenta importante de estudos futuros que avaliem o papel das glicoproteínas plaquetárias na predisposição individual a condições pró-trombóticas e resposta à terapia antitrombótica.</p>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Protein \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Polymorphism \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Primers \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Restriction enzymes \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GPIIIa \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pl<span class="elsevierStyleSup">A</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">F-GGACTTCTCTTTGGGCTCCTR-CTGTCTCCAGAGCCCTTGTC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">MspII</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GPIbα</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Kozak \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">F-AGGGGGATCCACTCAAGGR-AGGCGAGTGTAAGGCATCAG \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">BsuRI</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HPA-2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">F-GCCAGCCACCTAGAAGTGAAR-AAAAGCAAAAGGCAGGAGGT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Lwel</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">VNTR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">F-CTGGAGCCCACTCCAAGCR-TTGTGGCAGACACCAGGAT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GPIa \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">C807T \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">F-CTACCGGCCCATGTCTAAATR-TCTTTGTCTTTTCCTTACTTTTTCA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Hpy188I</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab272099.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Primers and restriction enzymes used for genotypic discrimination.</p>" ] ] 1 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Protein \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Polymorphism \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Genotypes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Genotypic frequenciesn (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Alleles \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Allelic frequencies \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GPIIIa \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pl<span class="elsevierStyleSup">A</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pl<span class="elsevierStyleSup">A1/A1</span>Pl<span class="elsevierStyleSup">A1/A2</span>Pl<span class="elsevierStyleSup">A2/A2</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">155 (68.3)61 (26.9)11 (4.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pl<span class="elsevierStyleSup">A1</span>Pl<span class="elsevierStyleSup">A2</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.8170.183 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GPIbα</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Kozak \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TTCTCC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">180 (79.3)46 (20.3)1 (0.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.8950.105 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HPA-2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">aaabbb \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">184 (81.1)43 (18.9)0 (0.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ab \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.9060.094 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">VNTR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BCBDCCCDDDCE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">35 (15.4)2 (0.9)160 (70.5)26 (11.5)3 (1.3)1 (0.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BCDE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.0810.8420.0750.002 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GPIa \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">C807T \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CCCTTT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">90 (39.7)114 (50.2)23 (10.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.6480.352 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab272098.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Genotypic and allelic frequencies of the five studied polymorphisms.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => 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Bamford" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Artioscler Thromb Vasc Biol" "fecha" => "1998" "volumen" => "7" "paginaInicial" => "1124" "paginaFinal" => "1131" ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:3 [ "identificador" => "xack45569" "titulo" => "Acknowledgements" "texto" => "<p id="par0070" class="elsevierStylePara elsevierViewall">This project was financially supported by <span class="elsevierStyleGrantSponsor">CESPU</span>, <span class="elsevierStyleGrantSponsor" id="gs0005">CRL</span> (<span class="elsevierStyleGrantNumber" refid="gs0005">AL/12/2006/CESPU</span>, <span class="elsevierStyleGrantNumber" refid="gs0005">AL/11/2007/CESPU</span> and <span class="elsevierStyleGrantNumber" refid="gs0005">CITS/05/2009/CESPU</span>).</p>" ] ] ] "idiomaDefecto" => "en" "url" => "/21742049/0000003200000002/v1_201305171228/S217420491300041X/v1_201305171228/en/main.assets" "Apartado" => array:4 [ "identificador" => "9917" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original Articles" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/21742049/0000003200000002/v1_201305171228/S217420491300041X/v1_201305171228/en/main.pdf?idApp=UINPBA00004E&text.app=https://revportcardiol.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S217420491300041X?idApp=UINPBA00004E" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 4 | 4 | 8 |
| 2024 October | 25 | 26 | 51 |
| 2024 September | 41 | 22 | 63 |
| 2024 August | 34 | 30 | 64 |
| 2024 July | 27 | 29 | 56 |
| 2024 June | 34 | 19 | 53 |
| 2024 May | 27 | 18 | 45 |
| 2024 April | 21 | 26 | 47 |
| 2024 March | 28 | 15 | 43 |
| 2024 February | 23 | 23 | 46 |
| 2024 January | 26 | 22 | 48 |
| 2023 December | 20 | 23 | 43 |
| 2023 November | 22 | 18 | 40 |
| 2023 October | 19 | 14 | 33 |
| 2023 September | 21 | 24 | 45 |
| 2023 August | 20 | 22 | 42 |
| 2023 July | 20 | 13 | 33 |
| 2023 June | 25 | 12 | 37 |
| 2023 May | 31 | 19 | 50 |
| 2023 April | 11 | 10 | 21 |
| 2023 March | 20 | 14 | 34 |
| 2023 February | 25 | 28 | 53 |
| 2023 January | 16 | 8 | 24 |
| 2022 December | 24 | 19 | 43 |
| 2022 November | 31 | 19 | 50 |
| 2022 October | 18 | 29 | 47 |
| 2022 September | 22 | 30 | 52 |
| 2022 August | 16 | 32 | 48 |
| 2022 July | 20 | 22 | 42 |
| 2022 June | 19 | 18 | 37 |
| 2022 May | 11 | 34 | 45 |
| 2022 April | 25 | 21 | 46 |
| 2022 March | 14 | 27 | 41 |
| 2022 February | 19 | 13 | 32 |
| 2022 January | 23 | 26 | 49 |
| 2021 December | 12 | 19 | 31 |
| 2021 November | 33 | 42 | 75 |
| 2021 October | 32 | 44 | 76 |
| 2021 September | 17 | 30 | 47 |
| 2021 August | 30 | 33 | 63 |
| 2021 July | 17 | 33 | 50 |
| 2021 June | 13 | 15 | 28 |
| 2021 May | 24 | 29 | 53 |
| 2021 April | 37 | 51 | 88 |
| 2021 March | 44 | 10 | 54 |
| 2021 February | 46 | 13 | 59 |
| 2021 January | 20 | 15 | 35 |
| 2020 December | 23 | 7 | 30 |
| 2020 November | 23 | 16 | 39 |
| 2020 October | 20 | 3 | 23 |
| 2020 September | 32 | 6 | 38 |
| 2020 August | 24 | 4 | 28 |
| 2020 July | 44 | 7 | 51 |
| 2020 June | 27 | 2 | 29 |
| 2020 May | 31 | 4 | 35 |
| 2020 April | 29 | 12 | 41 |
| 2020 March | 38 | 5 | 43 |
| 2020 February | 71 | 31 | 102 |
| 2020 January | 24 | 5 | 29 |
| 2019 December | 28 | 5 | 33 |
| 2019 November | 25 | 4 | 29 |
| 2019 October | 30 | 3 | 33 |
| 2019 September | 16 | 12 | 28 |
| 2019 August | 31 | 7 | 38 |
| 2019 July | 34 | 12 | 46 |
| 2019 June | 38 | 5 | 43 |
| 2019 May | 29 | 9 | 38 |
| 2019 April | 35 | 13 | 48 |
| 2019 March | 93 | 10 | 103 |
| 2019 February | 58 | 13 | 71 |
| 2019 January | 14 | 6 | 20 |
| 2018 December | 27 | 5 | 32 |
| 2018 November | 192 | 9 | 201 |
| 2018 October | 466 | 16 | 482 |
| 2018 September | 115 | 16 | 131 |
| 2018 August | 133 | 8 | 141 |
| 2018 July | 43 | 4 | 47 |
| 2018 June | 62 | 7 | 69 |
| 2018 May | 68 | 11 | 79 |
| 2018 April | 50 | 9 | 59 |
| 2018 March | 41 | 3 | 44 |
| 2018 February | 38 | 5 | 43 |
| 2018 January | 36 | 6 | 42 |
| 2017 December | 56 | 10 | 66 |
| 2017 November | 31 | 10 | 41 |
| 2017 October | 42 | 14 | 56 |
| 2017 September | 22 | 10 | 32 |
| 2017 August | 26 | 10 | 36 |
| 2017 July | 18 | 5 | 23 |
| 2017 June | 35 | 14 | 49 |
| 2017 May | 41 | 4 | 45 |
| 2017 April | 24 | 6 | 30 |
| 2017 March | 28 | 45 | 73 |
| 2017 February | 30 | 3 | 33 |
| 2017 January | 24 | 1 | 25 |
| 2016 December | 47 | 9 | 56 |
| 2016 November | 26 | 3 | 29 |
| 2016 October | 22 | 3 | 25 |
| 2016 September | 16 | 10 | 26 |
| 2016 August | 8 | 0 | 8 |
| 2016 July | 13 | 1 | 14 |
| 2016 June | 14 | 3 | 17 |
| 2016 May | 13 | 5 | 18 |
| 2016 April | 13 | 1 | 14 |
| 2016 March | 18 | 6 | 24 |
| 2016 February | 24 | 16 | 40 |
| 2016 January | 29 | 5 | 34 |
| 2015 December | 26 | 12 | 38 |
| 2015 November | 20 | 12 | 32 |
| 2015 October | 26 | 6 | 32 |
| 2015 September | 27 | 5 | 32 |
| 2015 August | 19 | 10 | 29 |
| 2015 July | 16 | 9 | 25 |
| 2015 June | 5 | 4 | 9 |
| 2015 May | 19 | 5 | 24 |
| 2015 April | 11 | 10 | 21 |
| 2015 March | 26 | 3 | 29 |
| 2015 February | 15 | 5 | 20 |
| 2015 January | 39 | 4 | 43 |
| 2014 December | 23 | 9 | 32 |
| 2014 November | 25 | 2 | 27 |
| 2014 October | 18 | 5 | 23 |
| 2014 September | 27 | 6 | 33 |
| 2014 August | 30 | 5 | 35 |
| 2014 July | 32 | 9 | 41 |
| 2014 June | 23 | 3 | 26 |
| 2014 May | 27 | 7 | 34 |
| 2014 April | 22 | 2 | 24 |
| 2014 March | 46 | 13 | 59 |
| 2014 February | 33 | 7 | 40 |
| 2014 January | 49 | 14 | 63 |
| 2013 December | 29 | 5 | 34 |
| 2013 November | 40 | 13 | 53 |
| 2013 October | 31 | 8 | 39 |
| 2013 September | 43 | 11 | 54 |
| 2013 August | 41 | 12 | 53 |
| 2013 July | 41 | 12 | 53 |
| 2013 June | 25 | 5 | 30 |
| 2013 May | 30 | 8 | 38 |
| 2013 April | 40 | 12 | 52 |
| 2013 March | 31 | 9 | 40 |
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