TITLE

GENETIC EVIDENCE FOR INTERACTION OF THE 5Q31 CYTOKINE LOCUS AND THE CARD15 GENE IN CROHN'S DISEASE

AUTHOR(S)
Mirza, M.M.; Fisher, S.A.; King, K.; Cuthbert, A.P.; Hampe, J.; Sanderson, J.; Mansfield, J.; Donaldson, P.; Macpherson, A.; Forbes, A.; Schreiber, S.; Lewis, C.M.; Mathew, C.G.
PUB. DATE
April 2003
SOURCE
Gut;Apr2003 Supplement 1, Vol. 52, pA60
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
A common haplotype containing 11 single nucleotide polymorphisms (SNPs) and spanning 250kb in the cytokine gene cluster on chromosome 5q31 has recently been reported to be strongly associated with Crohn's disease (CD) in Canadian families. We analysed 2 SNPs from this haplotype (C2063G and C2198G) in 267 individuals, and found them to be in strong linkage disequilibrium (D'=0.91). The C2063G SNP was then genotyped in Northern European IBD families which contained a total of 511 offspring affected with CD and 320 with ulcerative colitis (UC). Excess transmission of the 2063G allele was observed in CD (p=0.011) but not in UC. Genotyping of C2063G in an independent set of unrelated British cases with CD (n = 684) and UC (n = 388) and in 701 British controls showed that the 2063G allele was present at a significantly higher frequency in CD cases than in controls (p=0.008), but was not increased in UC. However, the increase in disease risk was small (odds ratio 1.49 for homozygotes, 95% CI: 1.11-2.0). The disease risk haplotype frequency was significantly elevated in 943 CD patients who also carried mutations in the CD susceptibility gene CARD15 (p=0.0018). Kaplan-Meier survival analysis of age of disease onset showed a significantly earlier onset in homozygotes for the 5q31 risk haplotype (p=0.0019). These findings suggest that genetic variants at the 5q31 (IBD5) locus may hasten the onset of Crohn disease, and co-operate with CARD 15 in disease causation.
ACCESSION #
9747695

 

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