RGD Reference Report - The Fc gamma receptor IIa R131H polymorphism is associated with inhibitor development in severe hemophilia A. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models   new Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources

The Fc gamma receptor IIa R131H polymorphism is associated with inhibitor development in severe hemophilia A.

Authors: Eckhardt, CL  Astermark, J  Nagelkerke, SQ  Geissler, J  Tanck, MW  Peters, M  Fijnvandraat, K  Kuijpers, TW 
Citation: Eckhardt CL, etal., J Thromb Haemost. 2014 Aug;12(8):1294-301. doi: 10.1111/jth.12631. Epub 2014 Jul 16.
RGD ID: 11040767
Pubmed: PMID:24916518   (View Abstract at PubMed)
DOI: DOI:10.1111/jth.12631   (Journal Full-text)

BACKGROUND: The development of factor (F) VIII neutralizing alloantibodies (inhibitors) is a major complication of treatment with FVIII concentrates in hemophilia A and the etiology is still poorly understood. The low-affinity Fc gamma receptors (FcgammaR), which are expressed on immune cells, provide an important link between cellular and humoral immunity by interacting with IgG subtypes. Genetic variations of the genes encoding FcgammaRs (FCGR genes) have been associated with susceptibility to infectious and autoimmune diseases. OBJECTIVES: The aim of this study was to investigate the association between genetic variation of FCGR and inhibitor development in severe hemophilia A. PATIENTS/METHODS: In this case-control study samples of 85 severe hemophilia A patients (siblings from 44 families) were included. Single nucleotide polymorphisms and copy number variation of the FCGR2 and FCGR3 gene cluster were studied in an FCGR-specific multiplex ligation-dependent probe amplification assay. Frequencies were compared in a generalized estimating equation regression model. RESULTS: Thirty-six patients (42%) had a positive history of inhibitor development. The polymorphism 131R > H in the FCGR2A gene was associated with an increased risk of inhibitor development (odds ratio [OR] per H-allele, 1.8; 95% confidence interval [CI], 1.1-2.9). This association persisted in 29 patients with high titer inhibitors (OR per H-allele, 1.9; 95% CI, 1.2-3.2) and in 44 patients with the F8 intron 22 inversion (OR per H-allele, 2.6; 95% CI, 1.1-6.6). CONCLUSIONS: Hemophilia A patients with the HH genotype of the FCGR2A polymorphism 131R > H have a more than 3-fold increased risk of inhibitor development compared with patients with the RR genotype.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
factor VIII deficiency susceptibilityIAGP 11040767DNA:SNP:cds:p.R131H (human)RGD 
factor VIII deficiency susceptibilityISOFCGR2A (Homo sapiens)11040767; 11040767DNA:SNP:cds:p.R131H (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Fcgr2a  (Fc gamma receptor 2A)

Genes (Mus musculus)
Fcgr3  (Fc receptor, IgG, low affinity III)

Genes (Homo sapiens)
FCGR2A  (Fc gamma receptor IIa)


Additional Information