Disease relevance of HPSE2

• Platelets from two patients with the Bernard-Soulier syndrome (BSS) were HPA-2(a-,b-) in the immunofluorescence test with HPA-2 alloantibodies on chloroquine-treated platelets [1].
• Threonine-145/methionine-145 variants of baculovirus produced recombinant ligand binding domain of GPIbalpha express HPA-2 epitopes and show equal binding of von Willebrand factor [2].
• Stepwise cloning and molecular characterization of the HgiDI restriction-modification system from Herpetosiphon giganteus Hpa2 [3].
• Polymorphisms (VNTR and HPA-2) in this receptor are associated with increased risk of coronary heart disease (CHD) and cerebral vascular disease (CVD) [4].
• Alloimmunization against human platelet antigen 2 (HPA2) in a series of multi-transfused beta-thalassemia patients [5].

High impact information on HPSE2

• Previously, we have established that an antigenic polymorphism of platelets, the HPA-2 or Ko alloantigen system, is located on the 45-kD amino-terminal globular domain of GPIb alpha [6].
• DNA-typing for the HPA-2 alloantigen system on genomic DNA obtained from a small number of cells may be applied for determining the genotype of a fetus from an immunized mother or of severely thrombocytopenic patients [6].
• NH2-terminal globular domain of human platelet glycoprotein Ib alpha has a methionine 145/threonine145 amino acid polymorphism, which is associated with the HPA-2 (Ko) alloantigens [6].
• Restriction fragment length polymorphism analysis of the amplified DNA of 3 HPA-2(a-,b+), 2 HPA-2(a+,b+), and 11 HPA-2(a+,b-) donors showed that these restriction sites were associated with the HPA-2 alleles [6].
• Our data are compatible with an involvement of the leucine-rich repeat domain of GPIbalpha in vWF binding and indicate that recombinant GPIbalpha may be used to detect HPA-2 antibodies [2].

Chemical compound and disease context of HPSE2

• Platelet polymorphisms (Kozak, VNTR and HPA-2) within glycoprotein (GP)Ib alpha may be associated with an increased risk of arterial thrombosis [7].

Biological context of HPSE2

• Alternative splicing of the hpa2 transcript yields three different mRNAs, encoding putative proteins of 480, 534, and 592 amino acids [8].
• Two polymorphisms (HPA-2 and VNTR) that affect phenotype have been described in GPIbalpha [9].
• To determine the gene frequencies for the HPA-1, HPA-2 and HPA-3 systems directly, DNA from 98 of these donors was isolated from peripheral blood mononuclear leucocytes and specific fragments were amplified by polymerase chain reaction (PCR) [10].
• HPA-2 arises from a threonine/methionine dimorphism at residue 145 of the GPIb alpha sequence, whereas different numbers of tandem repeats of a 39-bp sequence encoding 13-amino acids corresponding to a region between serine399 and threonine411 of the GPIb alpha account for the latter [11].
• Although the nucleotide and deduced amino acid sequences of these cDNAs are almost identical, the deduced HPR1 protein contains Ser-Lys-Leu at its carboxy-terminal end, which is known as a microbody-targeting signal, while the deduced HPR2 protein does not [12].

Anatomical context of HPSE2

• A larger study is required, however, to determine whether HPA-2 is a novel risk factor for branch retinal vein occlusion [13].
• From the sequences of the two HPR cDNAs, the HPR1 protein, but not the HPR2 protein, was found to have a targeting sequence into peroxisomes at the carboxy terminus [14].

Regulatory relationships of HPSE2

• von Willebrand factor but not alpha-thrombin binding to platelet glycoprotein Ibalpha is influenced by the HPA-2 polymorphism [15].

Other interactions of HPSE2

• Cloning and expression profiling of Hpa2, a novel mammalian heparanase family member [8].
• We studied haplotypes of ITGA2 defined by single nucleotide substitutions at positions -52, 807, and 1648, and GP1BA variants defined by sequence changes in positions -5 (Kozak), 1018 (T145M, HPA-2) and 1285 (VNTR A, B, C and D) [16].
• CONCLUSIONS: Our results indicate that the HPA-1, HPA-2, HPA-3, and HPA-5 polymorphisms are not associated with an increased risk for stroke [17].
• Only two antigenic polymorphisms have thus far been established in these proteins: the HPA-2 in GP Ib alpha and the rare Iy variant in GP Ib beta [18].

Analytical, diagnostic and therapeutic context of HPSE2

• Sequence analyses predict that all three Hpa2 proteins are intracellular, membrane-bound enzymes [8].
• Prolactin was measured in 472 patients 1 day before (Hpr1) and in 457 patients 10 days after (Hpr2) mastectomy [19].
• The purpose of present study was to investigate the association between gene polymorphism of GP I balpha (human platelet antigen 2, HPA2) and ischemic stroke in a matched case-control study [20].
• MATERIALS AND METHODS: Using allele-specific restriction enzyme analysis, we studied the distribution of HPA-1 and HPA-2 alleles in six Brazilian Amazon tribes of Amerindians, belonging to five different language stocks [21].
• Genotyping for GP I balpha polymorphism was documented by polymerase chain reaction amplification and restriction enzyme analysis.There were no statistically significant differences in the GP I balpha HPA2 genotype distribution between ischemic stroke group, large-vessel subtype group, small-vessel subtype group and corresponding control groups [20].

References