Analysis of Platelet Glycoprotein Ia (α2 Integrin) Allele Frequencies in Three North American Populations Reveals Genetic Association between Nucleotide 807C/T and Amino Acid 505 Glu/Lys (HPA-5) Dimorphisms

Aramaki, Kaelen; Teramura, Gayle; Gaur, Lakshmi K.; Reiner, Alexander P.

doi:10.1055/s-0037-1615228

Cited by 30 publications

(4 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Samples for DNA extraction were collected in EDTA tubes and maintained at 4 °C until use. Genomic DNA was isolated from peripheral blood lymphocytes in accordance with the method of Miller et al 14 Platelet membrane glycoprotein Ia, Ibα, IIb and IIIa genotypes were analyzed by means of amplification of DNA using the polymerase chain reaction (PCR), as described in previously published methods, 15 , 16 , 17 and using the oligonucleotide sequencing primers described in Table 1 . The mutations analyzed were selected because these mutations present high frequency in our population.…”

Section: Methodsmentioning

confidence: 99%

“…Genotyping of glycoprotein Ia ( 807C/T ) polymorphism was performed by means of enzymatic digestion of a 115 bp fragment using Taq I at 37 °C, overnight, followed by identification of the fragments by means of electrophoresis on 2.5% agarose gel. 15 Presence of the 92 bp fragment indicates homozygosis of the wild genotype (C/C), while presence of the 115 bp fragment indicates homozygosis of the mutant allele.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Gene mutations of platelet glycoproteins and response to tirofiban in acute coronary syndrome

et al. 2016

View full text Add to dashboard Cite

CONTEXT AND OBJECTIVES: Glycoprotein inhibitors (abciximab, eptifibatide and tirofiban) are used in patients with unstable angina and non-ST-segment elevation myocardial infarction before percutaneous coronary intervention. Of these, tirofiban is the least effective. We hypothesized that the response to tirofiban might be associated with glycoprotein gene mutations. DESIGN AND SETTING: Prospective study at Emergency Unit, Heart Institute (InCor), University of São Paulo. METHOD: Intrahospital evolution and platelet aggregation in response to tirofiban were analyzed in relation to four glycoprotein mutations in 50 patients indicated for percutaneous coronary intervention: 17 (34%) with unstable angina and 33 (66%) with non-ST-segment elevation myocardial infarction. Platelet aggregation was analyzed using the Born method. Blood samples were obtained before and one hour after tirofiban infusion. Glycoproteins Ia (807C/T), Ib (Thr/Met), IIb (Ile/Ser) and IIIa (PIA) were the mutations selected. RESULTS: Hypertension, dyslipidemia, diabetes, smoking, previous coronary artery disease and stroke were similar between the groups. Mutant glycoprotein IIIa genotypes had lower platelet aggregation before tirofiban administration than that of the wild genotype (41.0% ± 22.1% versus 55.9% ± 20.8%; P = 0.035). Mutant glycoprotein IIIa genotypes correlated moderately with lower platelet inhibition (r = -0.31; P = 0.030). After tirofiban administration, platelet glycoprotein Ia, Ib, IIb and IIIa mutations did not influence the degree of inhibition of platelet aggregation or intrahospital mortality. CONCLUSIONS: Mutations of glycoproteins Ia, Ib, IIb and IIIa did not influence platelet aggregation in response to tirofiban in patients with unstable angina and non-ST-segment elevation myocardial infarction. RESUMO CONTEXTO E OBJETIVOS:Inibidores da glicoproteína (abciximab, eptifibatide, tirofiban) são utilizados em pacientes com angina instável e infarto do miocárdio sem elevação do segmento ST (IAMSSST) antes da intervenção coronária percutânea. Dentre eles, o tirofiban é o menos eficaz. Nossa hipótese é que a resposta ao tirofiban possa estar associada a mutações no gene da glicoproteína. DESENHO E LOCAL: Estudo prospectivo na Unidade de Emergência do Instituto do Coração (InCor), Universidade de São Paulo (USP).MÉTODOS: Foram analisadas a evolução intra-hospitalar e agregabilidade plaquetária em resposta ao tirofiban de 4 mutações da glicoproteína em 50 pacientes com indicação para intervenção coronária percutânea, 17 (34%) com angina instável e 33 (66%) com IAMSSST. A agregação plaquetária foi analisada pelo método de Born. Amostras de sangue foram obtidas antes e uma hora após infusão do tirofiban. As glicoproteínas Ia (807C/T), Ib (Thr/Met), IIb (Ile/Ser) e IIIa (PIA) foram as mutações selecionadas. RESULTADOS: Hipertensão, dislipidemia, diabetes, tabagismo, doença coronariana e acidente vascular cerebral prévios foram semelhantes entre os grupos. Observou-se menor agregabilidade plaquetária dos genótipos mutantes da...

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Gene mutations of platelet glycoproteins and response to tirofiban in acute coronary syndrome

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Genotyping of the 6 HPA polymorphisms [HPA-1 T196C, HPA-2 T524C, HPA-3 T2622G, HPA-4 G526A, HPA-5 G1648A & HPA-15 A2108C (22)] was performed by Sequence-Specific Primers PCR (PCR-SSP), as described previously (23) with slight modifications. Briefly, to perform the PCR-SSP assay, the kit was used in such a way that 10 µl of Red master mix amplicon (Taq polymerase 2x and Mgcl 2 1.5 µM) and 1 µl of forward primer, 1 µl of reverse primer, 4 µl of water and 4 µl of DNA Template were mixed and vortexed.…”

Section: Sequence-specific Primers Pcrmentioning

confidence: 99%

“…Since the frequencies of different HPA genes vary in different populations, MAIPA for different IgG antibodies against HPA-1, -2, -3, -4, -5, and -15 is needed. HPA-1, HPA-3, and HPA-4 are present on the GPIIb/IIIa, while HPA-2 is found on the GPIb/IX, HPA-5 is carried on the GPIa/IIa, and HPA-15 is localized to CD109 (22). MAIPA assay is an enzyme-linked immunosorbent assay (ELISA) technique for the detection and identification of HPA antibodies.…”

Section: Detection Of Plts Associated Antibodiesmentioning

confidence: 99%

Association of the human platelet antigens polymorphisms with platelet count in patients with COVID-19

Ghaffari,

Rad,

Moradi Hasan-Abad

et al. 2023

Front. Med.

View full text Add to dashboard Cite

Polymorphism in human platelet antigen (HPA)-1 and HPA-3 (GPIIb/IIIa), HPA-2 (GPIb/IX), HPA-4 (GPIIIa), HPA-5 (GPIa/IIa), & HPA-15 (CD109) was investigated in 86 COVID-19-infected patients with thrombocytopenia (Group A) and 136 COVID-19-infected patients without thrombocytopenia (Group B). HPA genotyping was done by the sequence-specific primers PCR method. Lower HPA-3a and higher HPA-3b (P = 0.028) allele frequencies were seen in Group A than in Group B, and homozygosity for HPA 3b (P = 0.038) alleles was more prevalent in Group A than in Group B. The allele and genotype distributions of the other HPA polymorphic variants were similar between the two groups. Univariate analysis identified the CCGGGC (P = 0.016) combined genotype to be negatively associated & the TCGGGC (P = 0.003) and CCGGGC (P = 0.003) to be positively associated with thrombocytopenia. The frequency of anti-HPA-1a and anti-HPA-3a antibodies was significantly higher in all patients compared to other anti-HPAs antibodies (P < 0.05). These results highlight the role of HPAs in the thrombocytopenia of COVID-19 infected patients. This is the first evidence demonstrating the differential association of the six common HPA gene variants and specific HPA genotype combinations with thrombocytopenia in COVID-19-infected patients.

show abstract

Polymorphisms of the human platelet alloantigens HPA‐1, HPA‐2, HPA‐3, and HPA‐4 in ischemic stroke

et al. 2008

View full text Add to dashboard Cite

Polymorphism in human platelet antigen (HPA)-1 and HPA-3 (GPIIb/IIIa), HPA-2 (GPIb/IX), HPA-4 (GPIIIa), and HPA-5 (GPIa/IIa) was investigated in 329 stroke patients and 444 matched control subjects. HPA genotyping was done by PCR-SSP method. Lower HPA-1a (P < 0.001) and higher HPA-1b (P < 0.001) allele frequencies were seen in patients than control subjects, and homozygosity for HPA-1b (P < 0.001) alleles was more prevalent in stroke cases than in controls. The allele and genotype distributions of the other HPA polymorphic variants were similar between cases and controls. Select HPA combined genotypes comprising the 2121 (Pc 5 0.008) and 2221 (Pc 5 0.018) genotypes, which were positively associated, and the 1111 (Pc < 0.001), which was negatively associated with stroke, thereby conferred a disease susceptibility and protective nature to these genotype combinations. Multivariate analysis confirmed the negative association of the 1111 (P < 0.001) and the positive association of the 2121 (P 5 0.017) combined genotypes with stroke, after adjustment for a number of covariates. This is the first evidence demonstrating differential association of the common 4 HPA gene variants and specific HPA genotype combinations with stroke. Am. J. Hematol. 83:570-573, 2008. V

show abstract

Analysis of Platelet Glycoprotein Ia (α2 Integrin) Allele Frequencies in Three North American Populations Reveals Genetic Association between Nucleotide 807C/T and Amino Acid 505 Glu/Lys (HPA-5) Dimorphisms

Cited by 30 publications

References 34 publications

Gene mutations of platelet glycoproteins and response to tirofiban in acute coronary syndrome

Gene mutations of platelet glycoproteins and response to tirofiban in acute coronary syndrome

Association of the human platelet antigens polymorphisms with platelet count in patients with COVID-19

Polymorphisms of the human platelet alloantigens HPA‐1, HPA‐2, HPA‐3, and HPA‐4 in ischemic stroke

Contact Info

Product

Resources

About