1. ¹Department of Biochemistry, University of Otago, Dunedin, New Zealand
2. ²Cambridge Institute for Medical Research, Addenbrooke's Hospital, UK
3. ³Department of Medicine, Birmingham Heartlands Hospital, UK
4. ⁴Institute of Human Genetics, University of Newcastle, UK
5. ⁵Department of Pathology, University of Otago, Dunedin, New Zealand
6. ⁶Department of Medicine, University of Auckland, New Zealand
7. ⁷Department of Paediatrics, Christchurch Hospital, New Zealand
8. ⁸Department of Rheumatology, Middlemore Hospital, Auckland, New Zealand
9. ⁹Wellington School of Medicine and Health Sciences, New Zealand
10. ¹⁰Department of Medicine, University of Otago, Dunedin, New Zealand
11. ¹¹Department of Endocrinology, Christchurch Hospital, New Zealand
12. ¹²Department of Endocrinology, Dunedin Hospital, Dunedin, New Zealand
13. ¹³Department of Molecular Medicine, University of Auckland, New Zealand
14. ¹⁴Lipid and Diabetes Research Group, Christchurch Hospital, New Zealand
15. ¹⁵Department of Paediatrics, Dunedin Hospital, Dunedin, New Zealand
16. ¹⁶Department of Rheumatology, Auckland Hospital, New Zealand

Correspondence: Dr T Merriman, Department of Biochemistry, University of Otago, Dunedin, New Zealand. Tel: +64 3 4795 798; Fax: +64 3 4797 866; E-mail: tony.merriman@stonebow.otago.ac.nz

Received 18 February 2003; Revised 29 April 2003; Accepted 10 June 2003.

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.