The deleted in colorectal carcinoma (DCC) gene 201 R --> G polymorphism: no evidence for genetic association with autoimmune disease.
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.
Hall
Richard J
RJ
Department of Biochemistry, University of Otago, Dunedin, New Zealand.
Merriman
Marilyn E
ME
Green
Rachel A
RA
Markham
Valerie H
VH
Smyth
Deborah J
DJ
Heward
Joanne M
JM
Jennings
Claire E
CE
Braithwaite
Antony W
AW
Cundy
Tim
T
Darlow
Brian A
BA
Gow
Peter J
PJ
Harrison
Andrew A
AA
Highton
John
J
Hunt
Penny J
PJ
Manning
Patrick
P
Pokorny
Violetta
V
Scott
Russell S
RS
Taylor
Barry J
BJ
Willis
Jinny A
JA
Yeoman
Sue
S
McLean
Lachy
L
Gough
Stephen C L
SC
Pearce
Simon H
SH
Merriman
Tony R
TR
D000328:Adult; D017668:Age of Onset; D001327:Autoimmune Diseases / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015179:Colorectal Neoplasms / Q000235:genetics*; D016163:Genes, DCC; D005828:Genetics, Population; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D018895:Microsatellite Repeats; D011110:Polymorphism, Genetic