Abstract
The product of the deleted in colorectal carcinoma (DCC) gene has a role in apoptosis and is a positional candidate for IDDM6, the putative chromosome 18q12–q23 autoimmune disease locus. We hypothesised that a nonconservative substitution (DCC 201 R → G; nucleotide (nt) 601 C → G), located in an extracellular immunoglobulin-like domain of DCC, is an aetiological determinant of autoimmunity. We tested this hypothesis by genetically testing the nt 601 C → G polymorphism for association with three autoimmune phenotypes in a large population-based case–control study. There was no evidence for association of DCC nt 601 C → G with autoimmune disease in cohorts comprising 2253 subjects with rheumatoid arthritis, type I diabetes and Graves' disease, and 2225 control subjects, from New Zealand and the United Kingdom. Furthermore, using the transmission disequilibrium test, there was no significant evidence for biased transmission of the nt 601 C → G polymorphism to probands within a 382 family type I diabetes affected sibpair cohort from the United Kingdom. Thus, the DCC 201 R → G polymorphism does not appreciably influence risk of developing the autoimmune diseases tested.
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Acknowledgements
The New Zealand Health Research Council, New Zealand Lottery Grants Board, the University of Otago Dean's Bequest Fund, the Arthritis Foundation of New Zealand, the RG Bell Charitable Trust, the Juvenile Diabetes Research Foundation, and the Wellcome Trust are thanked for financial support. RJH was supported by a University of Otago Postgraduate Scholarship. Heather Cordell is thanked for advice, John Todd for generously providing access to clinical samples and laboratory facilities and review of the manuscript, Peter Jones (Queen Elizabeth Hospital for Rheumatic Disease and Rehabilitation, Rotorua, NZ) and Vivienne Field (Christchurch Hospital, New Zealand) for recruiting patients, and Richie Poulton (Director of the Dunedin Multidisciplinary Health and Development Study) for collaborating on this project.
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Hall, R., Merriman, M., Green, R. et al. The deleted in colorectal carcinoma (DCC) gene 201 R → G polymorphism: no evidence for genetic association with autoimmune disease. Eur J Hum Genet 11, 840–844 (2003). https://doi.org/10.1038/sj.ejhg.5201059
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DOI: https://doi.org/10.1038/sj.ejhg.5201059
