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 language | English |
|---|---|
| Pages (from-to) | 891-894 |
| Number of pages | 4 |
| Journal | Transfusion |
| Volume | 36 |
| Issue number | 10 |
| Publication status | Published - Oct 1996 |
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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 journal › Article
}
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.
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M3 - Article
C2 - 8863776
AN - SCOPUS:0029840990
VL - 36
SP - 891
EP - 894
JO - Transfusion
JF - Transfusion
SN - 0041-1132
IS - 10
ER -