Evidence that deletion at FCGR3B is a risk factor for systemic sclerosis

Autor: Tony R. Merriman, Roger Hesselstrand, V. Fonollosa, Norberto Ortego-Centeno, Cushla McKinney, Javier Martin, Gabriela Riemekasten, P. Airo, J. C. A. Broen, M. J. H. Coenen, Madelon C. Vonk, Patricia Carreira, L. Beretta, R. Scorza, C. P. Simeon, Trdj Radstake, M. A. Gonzalez-Gay, N. Hunzelmann
Rok vydání: 2012
Předmět:
DNA Copy Number Variations
Immunology
Centromere
Gene Dosage
Inflammation
Biology
GPI-Linked Proteins
White People
Risk Factors
Scleroderma
Limited
Gene cluster
Genetics
medicine
Humans
Copy-number variation
Risk factor
skin and connective tissue diseases
Genomic disorders and inherited multi-system disorders Molecular epidemiology [IGMD 3]
Genetics (clinical)
Genetic Association Studies
Autoantibodies
Scleroderma
Systemic
Base Sequence
Immune complex clearance
Receptors
IgG
FCGR3B
Infection and autoimmunity Auto-immunity
transplantation and immunotherapy [NCMLS 1]
Europe
DNA Topoisomerases
Type I
FCGR3B Gene
Case-Control Studies
Scleroderma
Diffuse
Evaluation of complex medical interventions Auto-immunity
transplantation and immunotherapy [NCEBP 2]
Gene polymorphism
medicine.symptom
DNA Probes
Gene Deletion
Zdroj: Genes and Immunity, 13, 6, pp. 458-60
Genes and Immunity, 13, 458-60
ISSN: 1466-4879
DOI: 10.1038/gene.2012.15
Popis: Contains fulltext : 107808.pdf (Publisher’s version ) (Closed access) There is increasing evidence that gene copy number (CN) variation influences clinical phenotype. The low-affinity Fc receptor 3B (FCGR3B) located in the FCGR gene cluster is a CN polymorphic gene involved in the recruitment of polymorphonuclear neutrophils to sites of inflammation and their activation. Given the genetic overlap between systemic lupus erythematosus and systemic sclerosis (SSc) and the strong evidence for FCGR3B CN in the pathology of SLE, we hypothesised that FCGR3B gene dosage influences susceptibility to SSc. We obtained FCGR3B deletion status in 777 European Caucasian cases and 1000 controls. There was an inverse relationship between FCGR3B CN and disease susceptibility. CN of /= 2. Although requiring replication, these results suggest that impaired immune complex clearance arising from FCGR3B deficiency contributes to the pathology of SSc, and FCGR3B CN variation is a common risk factor for systemic autoimmunity.
Databáze: OpenAIRE
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