Contribution of single nucleotide polymorphisms within FCRL3 and MAP3K7IP2 to the pathogenesis of Graves' disease

Simmonds, Matthew J., Heward, J. M., Carr-Smith, J. , Foxall, H., Franklyn, J. A. and Gough, S. C. L. (2006) Contribution of single nucleotide polymorphisms within FCRL3 and MAP3K7IP2 to the pathogenesis of Graves' disease. Journal of Clinical Endocrinology and Metabolism, 91 (3). pp. 1056-1061. ISSN 0021-972X

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Context: Recently six DNA variants, two of which (M55V and 001Msp) are present in nuclear factor-kappa inhibitors SUMO-4 and MAP3K7IP2 and four of which (fcrl3_3, fcrl3_4, fcrl3_5, and fcrl3_6) modulate nuclear factor-kappa binding and production of the B cell surface molecule FCRL3, have been reported to be associated with a number of autoimmune diseases. Objective: The aim of this study was to investigate the association of these polymorphisms with disease in a large UK Caucasian Graves' disease (GD) data set. Design: The study was a case-control association study of six polymorphisms. Setting: The study was conducted at a UK academic department of medicine. Patients or Participants: Study population included 1056 GD patients and 864 controls. Interventions: There were no interventions. Main Outcome Measures: Tests for association with disease were measured. Results: No association with disease was found for the M55V singlenucleotide polymorphism (SNP). Association was, however, found between GD and the 001Msp SNP odds ratio (OR) 1.19 (95% confidence interval CI]) 1.03-1.37], fcrl3_3 SNP OR 1.17 (95% CI 1.02-1.34), fcrl3_5 SNP OR 1.18 (95% CI 1.04-1.35), and fcrl3_6 SNP OR 1.20 (95% CI 1.05-1.36). The 001Msp SNP was found to be associated with the presence of TSH receptor autoantibodies OR 1.75 (95% CI 1.09-2.79). Conclusion: Functional evidence suggests that the 001Msp, fcrl3_3, fcrl3_5, and fcrl3_6 SNPs could cause changes in B cell signaling and activation pathways that could account for their association with GD. Further replication in independent data sets and fine mapping of the surrounding gene regions are needed to confirm the magnitude of the effect and location of the etiological variant(s) present within these gene regions.

Keywords:Fc receptor, I kappa B, immunoglobulin enhancer binding protein, protein FCRL3, protein MAP3K7IP2, sumo 4 protein, SUMO protein, unclassified drug, article, autoimmune disease, B lymphocyte, controlled study, gene location, gene mapping, Graves disease, human, major clinical study, priority journal, protein binding, signal transduction, single nucleotide polymorphism, United Kingdom, Adaptor Proteins, Signal Transducing, Base Sequence, DNA, DNA Primers, European Continental Ancestry Group, Genotype, Humans, Phenotype, Polymerase Chain Reaction, Polymorphism, Restriction Fragment Length, Polymorphism, Single Nucleotide, Receptors, Immunologic, Reference Values
Subjects:C Biological Sciences > C420 Human Genetics
Divisions:College of Science > School of Life Sciences
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ID Code:22630
Deposited On:01 Apr 2016 08:43

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