Association of FcGRIIa with Graves' disease: a potential role for dysregulated autoantibody clearance in disease onset/progression

Yesmin, K. and Hargreaves, C. and Newby, P. R. and Brand, O. J. and Heward, J. M. and Franklyn, J. A. and Gough, S. C. L. and Simmonds, M. J. (2010) Association of FcGRIIa with Graves' disease: a potential role for dysregulated autoantibody clearance in disease onset/progression. Clinical Endocrinology, 73 (1). pp. 119-125. ISSN 0300-0664

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Abstract

Objective Although autoantibody production is a key feature of autoimmunity, it is not known whether variation in autoantibody production and clearance pathways is involved in disease susceptibility. The Fc Gamma Receptor IIa (FcGRIIa) molecule is involved in the clearance of autoantibodies and a functional single nucleotide polymorphism (SNP), rs1801274, which has been shown to alter autoantibody clearance, has been associated with a number of autoimmune diseases (AIDs) including systemic lupus erythematosus and type 1 diabetes. This study aimed to determine whether FcGRIIa is associated with Graves' disease (GD) in the UK Caucasian population by Tag SNP screening common polymorphisms within the FcGRIIa region. Design A case control association study investigating nine Tag SNPs within FcGRIIa, which captured the majority of known common variation within this gene region. Patients A dataset comprising 2504 UK Caucasian GD patients and 2784 geographically matched controls taken from the 1958 British Birth cohort. Measurements We used the κ2-test to investigate association between the Tag SNPs and GD. Results Association between the rs1801274 (P= 0·003, OR = 1·12 95% CI = 1·03-1·22 and rs6427598 (P = 0·012, OR = 0·90 95% CI = 0·83-0·98) SNPs and GD was observed. No other SNPs showed association with GD. No associations were seen between any of the SNPs investigated and specific GD clinical phenotypes. Conclusions This study suggests that variation in FcGRIIa predisposes to GD and further supports the role of FcGRIIa as a susceptibility locus for AIDs in general. © 2010 Blackwell Publishing Ltd.

Keywords:autoantibody, Fc receptor IIa, Fc receptor, Fc receptor IIa, antibody production, article, case control study, controlled study, disease course, gene frequency, genetic association, genetic variability, genotype, Graves disease, haplotype, human, immune dysregulation, major clinical study, phenotype, priority journal, single nucleotide polymorphism, genetic predisposition, genetics, immunology, metabolism, middle aged, Autoantibodies, Case-Control Studies, Disease Progression, Genetic Predisposition to Disease, Humans, Middle Aged, Polymorphism, Single Nucleotide, Receptors, IgG
Subjects:C Biological Sciences > C420 Human Genetics
Divisions:College of Science > School of Life Sciences
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ID Code:22613
Deposited On:12 Mar 2016 15:45

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