Frequency and functional relevance of genetic threonine 145/methionine 145 dimorphism in platelet glycoprotein Ibα in an Italian population

M. Mazzucato, P. Pradella, V. De Angelis, A. Steffan, L. De Marco

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Background: Threonine 145/methionine 145 dimorphism in platelet glycoprotein (GP) Ibα defines the human platelet antigen (HPA)-2 system that has been implicated in refractoriness to HLA-matched platelet transfusion and in neonatal immune thrombocytopenic purpura. Study Design and Methods: The occurrence of this amino acid dimorphism was investigated in 379 Italian blood donors by studying their genomic DNA. Two oligonucleotide primers, Ibα-3 (5'-GGACGTCTCCTTCAACCGGC-3') and Ibα-4 (5'-GCTTTGGTGGGGAACTTGAC-3'), were used in a polymerase chain reaction to generate a 591-base pair fragment that was digested with the restriction enzyme Acy I. To investigate whether this dimorphism is involved in the binding of von Willebrand factor (vWF) to GPIb, the binding of vWF to the GPIb/IX complex was measured in two Met 145/Met 145 and two Thr 145/Thr 145 subjects. Results: The genotypic frequencies are 78.9% for Thr/Thr, 19.8% for Thr/Met), and 1.3% for Met/Met; the allelic frequencies are 88.8% for Thr 145 and 11.2% for Met 145. Estimates for binding of subunit molecules per platelet at saturation and inhibition constant in mol per L, respectively, follow. In the presence of ristocetin (0.5 mg/mL), they are 11,460 ± 2,040 and 1.26 ± 0.44 x 10 -8 for normals and 11,230 ± 2,330 and 1.29 ± 0.48 x 10 -8 for patients. In the presence of botrocetin (2.5 μg/mL), they are 64,260 ± 7,760 and 2.99 ± 0.96 x 10 -8 for normals and 65,770 ± 11,570 and 2.47 ± 0.22 x 10 -8 for patients. Platelet aggregation responses obtained using platelet-rich plasma from donors with Met 145/Met 145 or Thr 145/Thr 145 genotype were within normal limits. Conclusion: Genotypic and phenotypic frequencies in the HPA-2 system in this population are consistent with those reported among the white population. Furthermore, the HPA-2 system is not involved in the binding of vWF to GPIb.

Original languageEnglish
Pages (from-to)891-894
Number of pages4
JournalTransfusion
Volume36
Issue number10
Publication statusPublished - Oct 1996

Fingerprint

Human Platelet Antigens
Platelet Glycoprotein GPIb-IX Complex
Platelet Membrane Glycoproteins
von Willebrand Factor
Threonine
Methionine
Ristocetin
Population
Platelet Transfusion
Platelet-Rich Plasma
DNA Primers
Idiopathic Thrombocytopenic Purpura
Blood Donors
Platelet Aggregation
Base Pairing
Blood Platelets
Genotype
Tissue Donors
Amino Acids
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Hematology
  • Immunology

Cite this

Frequency and functional relevance of genetic threonine 145/methionine 145 dimorphism in platelet glycoprotein Ibα in an Italian population. / Mazzucato, M.; Pradella, P.; De Angelis, V.; Steffan, A.; De Marco, L.

In: Transfusion, Vol. 36, No. 10, 10.1996, p. 891-894.

Research output: Contribution to journalArticle

@article{71064ff806ea47c9b7628af698a44006,
title = "Frequency and functional relevance of genetic threonine 145/methionine 145 dimorphism in platelet glycoprotein Ibα in an Italian population",
abstract = "Background: Threonine 145/methionine 145 dimorphism in platelet glycoprotein (GP) Ibα defines the human platelet antigen (HPA)-2 system that has been implicated in refractoriness to HLA-matched platelet transfusion and in neonatal immune thrombocytopenic purpura. Study Design and Methods: The occurrence of this amino acid dimorphism was investigated in 379 Italian blood donors by studying their genomic DNA. Two oligonucleotide primers, Ibα-3 (5'-GGACGTCTCCTTCAACCGGC-3') and Ibα-4 (5'-GCTTTGGTGGGGAACTTGAC-3'), were used in a polymerase chain reaction to generate a 591-base pair fragment that was digested with the restriction enzyme Acy I. To investigate whether this dimorphism is involved in the binding of von Willebrand factor (vWF) to GPIb, the binding of vWF to the GPIb/IX complex was measured in two Met 145/Met 145 and two Thr 145/Thr 145 subjects. Results: The genotypic frequencies are 78.9{\%} for Thr/Thr, 19.8{\%} for Thr/Met), and 1.3{\%} for Met/Met; the allelic frequencies are 88.8{\%} for Thr 145 and 11.2{\%} for Met 145. Estimates for binding of subunit molecules per platelet at saturation and inhibition constant in mol per L, respectively, follow. In the presence of ristocetin (0.5 mg/mL), they are 11,460 ± 2,040 and 1.26 ± 0.44 x 10 -8 for normals and 11,230 ± 2,330 and 1.29 ± 0.48 x 10 -8 for patients. In the presence of botrocetin (2.5 μg/mL), they are 64,260 ± 7,760 and 2.99 ± 0.96 x 10 -8 for normals and 65,770 ± 11,570 and 2.47 ± 0.22 x 10 -8 for patients. Platelet aggregation responses obtained using platelet-rich plasma from donors with Met 145/Met 145 or Thr 145/Thr 145 genotype were within normal limits. Conclusion: Genotypic and phenotypic frequencies in the HPA-2 system in this population are consistent with those reported among the white population. Furthermore, the HPA-2 system is not involved in the binding of vWF to GPIb.",
author = "M. Mazzucato and P. Pradella and {De Angelis}, V. and A. Steffan and {De Marco}, L.",
year = "1996",
month = "10",
language = "English",
volume = "36",
pages = "891--894",
journal = "Transfusion",
issn = "0041-1132",
publisher = "Blackwell Publishing Inc.",
number = "10",

}

TY - JOUR

T1 - Frequency and functional relevance of genetic threonine 145/methionine 145 dimorphism in platelet glycoprotein Ibα in an Italian population

AU - Mazzucato, M.

AU - Pradella, P.

AU - De Angelis, V.

AU - Steffan, A.

AU - De Marco, L.

PY - 1996/10

Y1 - 1996/10

N2 - Background: Threonine 145/methionine 145 dimorphism in platelet glycoprotein (GP) Ibα defines the human platelet antigen (HPA)-2 system that has been implicated in refractoriness to HLA-matched platelet transfusion and in neonatal immune thrombocytopenic purpura. Study Design and Methods: The occurrence of this amino acid dimorphism was investigated in 379 Italian blood donors by studying their genomic DNA. Two oligonucleotide primers, Ibα-3 (5'-GGACGTCTCCTTCAACCGGC-3') and Ibα-4 (5'-GCTTTGGTGGGGAACTTGAC-3'), were used in a polymerase chain reaction to generate a 591-base pair fragment that was digested with the restriction enzyme Acy I. To investigate whether this dimorphism is involved in the binding of von Willebrand factor (vWF) to GPIb, the binding of vWF to the GPIb/IX complex was measured in two Met 145/Met 145 and two Thr 145/Thr 145 subjects. Results: The genotypic frequencies are 78.9% for Thr/Thr, 19.8% for Thr/Met), and 1.3% for Met/Met; the allelic frequencies are 88.8% for Thr 145 and 11.2% for Met 145. Estimates for binding of subunit molecules per platelet at saturation and inhibition constant in mol per L, respectively, follow. In the presence of ristocetin (0.5 mg/mL), they are 11,460 ± 2,040 and 1.26 ± 0.44 x 10 -8 for normals and 11,230 ± 2,330 and 1.29 ± 0.48 x 10 -8 for patients. In the presence of botrocetin (2.5 μg/mL), they are 64,260 ± 7,760 and 2.99 ± 0.96 x 10 -8 for normals and 65,770 ± 11,570 and 2.47 ± 0.22 x 10 -8 for patients. Platelet aggregation responses obtained using platelet-rich plasma from donors with Met 145/Met 145 or Thr 145/Thr 145 genotype were within normal limits. Conclusion: Genotypic and phenotypic frequencies in the HPA-2 system in this population are consistent with those reported among the white population. Furthermore, the HPA-2 system is not involved in the binding of vWF to GPIb.

AB - Background: Threonine 145/methionine 145 dimorphism in platelet glycoprotein (GP) Ibα defines the human platelet antigen (HPA)-2 system that has been implicated in refractoriness to HLA-matched platelet transfusion and in neonatal immune thrombocytopenic purpura. Study Design and Methods: The occurrence of this amino acid dimorphism was investigated in 379 Italian blood donors by studying their genomic DNA. Two oligonucleotide primers, Ibα-3 (5'-GGACGTCTCCTTCAACCGGC-3') and Ibα-4 (5'-GCTTTGGTGGGGAACTTGAC-3'), were used in a polymerase chain reaction to generate a 591-base pair fragment that was digested with the restriction enzyme Acy I. To investigate whether this dimorphism is involved in the binding of von Willebrand factor (vWF) to GPIb, the binding of vWF to the GPIb/IX complex was measured in two Met 145/Met 145 and two Thr 145/Thr 145 subjects. Results: The genotypic frequencies are 78.9% for Thr/Thr, 19.8% for Thr/Met), and 1.3% for Met/Met; the allelic frequencies are 88.8% for Thr 145 and 11.2% for Met 145. Estimates for binding of subunit molecules per platelet at saturation and inhibition constant in mol per L, respectively, follow. In the presence of ristocetin (0.5 mg/mL), they are 11,460 ± 2,040 and 1.26 ± 0.44 x 10 -8 for normals and 11,230 ± 2,330 and 1.29 ± 0.48 x 10 -8 for patients. In the presence of botrocetin (2.5 μg/mL), they are 64,260 ± 7,760 and 2.99 ± 0.96 x 10 -8 for normals and 65,770 ± 11,570 and 2.47 ± 0.22 x 10 -8 for patients. Platelet aggregation responses obtained using platelet-rich plasma from donors with Met 145/Met 145 or Thr 145/Thr 145 genotype were within normal limits. Conclusion: Genotypic and phenotypic frequencies in the HPA-2 system in this population are consistent with those reported among the white population. Furthermore, the HPA-2 system is not involved in the binding of vWF to GPIb.

UR - http://www.scopus.com/inward/record.url?scp=0029840990&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029840990&partnerID=8YFLogxK

M3 - Article

C2 - 8863776

AN - SCOPUS:0029840990

VL - 36

SP - 891

EP - 894

JO - Transfusion

JF - Transfusion

SN - 0041-1132

IS - 10

ER -