Disease relevance of ITGB3

• We examined associations between 15 single nucleotide polymorphisms (SNPs) across ITGB3 and five CVD-related traits in the Hutterites: plasma levels of high density lipoprotein-cholesterol (HDL-c), triglycerides (TG), low density lipoprotein-cholesterol (LDL-c), and lipoprotein(a) [Lp(a)] and blood pressure or hypertension [1].
• In this report we describe the structure of the human beta subunit GPIIIa deduced from an analysis of 4.0 kb of overlapping cDNA sequences isolated from a human erythroleukemia (HEL) cell cDNA expression library [2].
• Overlapping genomic clones were isolated from cosmid and phage lambda libraries that contained the entire coding unit of the human gene for the mature GPIIIa protein [3].
• RESULTS: Basal platelet expression of CD61, CD42a and CD62P, and adenosine diphosphate-stimulated CD62P expression were increased in women with preeclampsia compared with normotensive pregnant women [4].
• METHODS: The expression levels of CD61, CD63, and PAC-1 on platelet surfaces were assayed by flow cytometry in 86 patients with different stages of uremia before and after transplantation [5].

Psychiatry related information on ITGB3

• Evaluation of a CD61 MoAb method for enumeration of platelets in thrombocytopenic patients and its impact on the transfusion decision-making process [6].

High impact information on ITGB3

• To test the in vivo effectiveness of the IgM antiidiotype, thrombocytopenia was induced in mice with 25 microgram of affinity-purified anti-GPIIIa 49-66 (mouse GPIIIa has 83% homology with human GPIIIa and Fc receptors for human IgG1) [7].
• The recombinant His327 form of GPIIb was found to be fully capable of associating with GPIIIa, therefore the role of the calcium-binding domains in intersubunit association was further examined by constructing amino-terminal segments of GPIIb that ended before the first, second, and third calcium-binding domains [8].
• A point mutation (C to T) was localized in exon D (iv) of GPIIIa that resulted in an 214Arg to 214Trp amino acid substitution [9].
• It thus appears that amino acid 143 of GPIIIa is not only associated with Pen phenotype, but specifically controls the formation and expression of the Pen alloantigenic determinants [10].
• Interestingly, this polymorphic residue is located within the putative RGD binding site (residues 109-171) of GPIIIa [10].

Chemical compound and disease context of ITGB3

• We conclude that functional polymorphisms in integrin genes ITGA2 and ITGB3 influence the development and progression of breast cancer, respectively [11].
• A new platelet alloantigen, termed CA, has recently been implicated in a case of neonatal alloimmune thrombocytopenia (NATP) in a Filipino family in Canada. Maternal anti-CA serum reacted with glycoprotein (GP) IIIa and maintained its reactivity after removal of high mannose carbohydrate residues from GPIIIa [12].
• The disulfide-rich region of platelet glycoprotein (GP) IIIa contains hydrophilic peptide sequences that bind anti-GPIIIa autoantibodies from patients with immune thrombocytopenic purpura (ITP) [13].
• (2) Compared to non-CML controls, CML specimens at diagnosis showed an increased reticulin fibrosis and a decreased expression of CD61 on megakaryocytes and of CD31 on vessels and hemopoietic cells [14].
• The most immunogenic platelet alloantigen in thrombocytopenia is the leucine 33 form of GPIIIa [15].

Biological context of ITGB3

• Furthermore, the serotonin QTL on 17q that was identified previously in this population, integrin beta 3 (ITGB3), and a novel locus on 2q influence serotonin levels only in males, whereas linkage to a region on chromosome 6q is specific to females [16].
• METHODS AND MEASUREMENTS: We genotyped and performed association tests on 19 single nucleotide polymorphisms in ITGB3 in the Hutterites, a founder population, and in three outbred replication populations [17].
• Because both the Leu33Pro polymorphism and the serotonin system have been implicated in cardiovascular disease (CVD) risk and treatment response, we studied additional variation in ITGB3 and its relationship to intermediate phenotypes associated with CVD in the same population [1].
• We also show preliminary evidence that genotypes at the ITGB3 and SLC6A4 loci may interact to affect autism susceptibility (P=0.033) [18].
• The integrin beta3 (ITGB3) and serotonin transporter (SLC6A4) genes were both recently identified as male quantitative trait loci (QTLs) for serotonin levels and alleles of each have been associated with autism [18].

Anatomical context of ITGB3

• This physical proximity of GPIIb and GPIIIa may be involved in the concurrent expression of these proteins by megakaryocytes, and may result in linkage disequilibrium between these two genes, which would limit the use of restriction length polymorphisms in linkage studies of GPIIb/IIIa abnormalities in small kindreds [19].
• This indicates that the GPIIIa-containing heterodimers in platelets and endothelial cells are not identical structures, but are members of a subfamily within the human family of adhesion protein receptors sharing an identical beta subunit [2].
• Human mast cells derived from fetal liver cells cultured with stem cell factor express a functional CD51/CD61 (alpha v beta 3) integrin [20].
• Changes in the percentage of CD61- or CD62P-positive leukocytes were significantly greater during hemodialysis with RC than with PS [21].
• Immunohistochemical staining after exposure to PMA showed that the expression of the platelet-associated markers CD41 and CD61 was enhanced in all cell lines indicating possible differentiation along the megakaryocyte lineage [22].

Associations of ITGB3 with chemical compounds

• We therefore evaluated the integrin-beta3 gene (ITGB3), an integrin gene within an asthma linkage peak on chromosome 17, as a candidate for susceptibility to asthma- and atopy-related phenotypes [17].
• Variation in ITGB3 is associated with asthma and sensitization to mold allergen in four populations [17].
• CD markedly inhibited the assembly of the cytoskeletal core as well as GPIIIa retention, whereas MB resulted in a large Triton-insoluble residue which contained GPIIIa [23].
• This study was designed to determine the structure of the gene for glycoprotein (GP) GPIIIa, the beta-subunit of the platelet membrane GPIIb-IIIa complex [3].
• These included (i) the transmembrane spanning segment, (ii) the cytoplasmic region containing the potential phosphorylation sites, and (iii) the six domains in the NH2-terminal half of GPIIIa that are highly conserved between two other integrin beta-subunits [3].

Physical interactions of ITGB3

• There is evidence that fibrinogen itself binds to regions in the amino terminal portions of both GPIIb and GPIIIa and that the sites interacting with the fibrinogen gamma chain and with RGD-containing peptides are spatially distinct [24].
• The HEL GPIIIa sequence was compared with the sequences of the beta subunit for the human LFA-1/Mac-1/p150.95 complex and human endothelial cell GPIIIa, revealing a 38% similarity with the former and virtual identity with the latter [2].
• A novel homozygous mutation (1619delC) in GPIIb gene associated with Glanzmann thrombasthenia, the decay of GPIIb-mRNA and the synthesis of a truncated GPIIb unable to form complex with GPIIIa [25].
• Since neither neuraminidase- nor endoglycopeptidase F-treatment of GPIIIa had any significant effect on the binding of PSG3, this array must be located within the amino acid sequence of GPIIIa but not in the carbohydrate moiety [26].

Regulatory relationships of ITGB3

• Anti-ITGAV/ITGB3 antibodies significantly reduced the size of the capillary network (P < 0.05) on Matrigel and also suppressed TNF-induced apoptosis (P < 0.05) in TCL1 cells [27].
• In this study we investigated mechanisms of platelet interaction with von Willebrand factor (vWF) induced by activating anti-glycoprotein (GP)IIb-IIIa antibody CRC54 directed against LIBS (ligand-induced binding site epitope) in GPIIIa [28].
• The expression of CD61 did not alter during storage and the percentage of platelets expressing CD42b was > 88% in all units on day 7 [29].
• To determine how this mutation impaired GPIIb-IIIa expression, recombinant GPIIb containing the mutation was coexpressed with GPIIIa in COS-1 cells [30].
• The platelet population was specified by the antiglycoprotein IIIa (CD61) antibody and activated platelets by the anti-P selectin (CD62) antibody [31].

Other interactions of ITGB3

• None of them reacted with dissociated GPIIb or GPIIIa [32].
• Adhesion occurred in part through the CD61/CD51 receptor [20].
• Assembly and GPIIIa content of cytoskeletal core in platelets agglutinated with bovine von Willebrand factor [23].
• We found that polyclonal antibodies to the platelet GPIIb-IIIa complex, GPIIIa, and the human vitronectin receptor inhibited TSP-mediated cell adhesion by 63-68% [33].
• No effects on the integrin beta-chains CD29 and CD61 could be detected [34].

Analytical, diagnostic and therapeutic context of ITGB3

• To study the association between early fetal loss and the presence of the PLA2 polymorphism of the ITGB3 gene we conducted a case-control study on 98 cases (i.e., women in fertile age, who experienced at least one episode of early fetal loss) and 38 healthy controls [35].
• In particular, the strongest effect of the ITGB3 PL(A2) allele was expressed on the risk of occlusion after revascularization procedures, mainly after stent implantation, a condition in which platelet activation is more important as compared with other stenotic mechanisms [36].
• The radiation hybrid panel indicates that the most likely position of human CDC27 on human chromosomes 17 is between the marker D17S409 and the beta 3 subunit of integrin (ITGB3) [37].
• Northern blot analysis using RNA from both HEL and endothelial cells revealed two GPIIIa transcripts of 5.9 and 4.1 kb [2].
• Immunoprecipitation of radiolabeled platelets using polyclonal anti-FXIII A-chain antibody identified two proteins corresponding to GPIIb and GPIIIa [38].

References