Contribution of the IL-2 and IL-10 genes to inflammatory bowel disease (IBD) susceptibility

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Abstract
Although the importance of genetic susceptibility to IBD has been established by epidemiological studies, the genes involved remain poorly characterized. Important candidate genes include those encoding the immunoregulatory cytokines IL-2 and IL-10. The aim of this study was to assess the contribution of the IL-2 and IL-10 genes to IBD susceptibility. One hundred and ninety-eight pairs of siblings with IBD were genotyped at dinucleotide repeat polymorphisms within the IL-2 and IL-10 genes, and data analysed by the affected sib-pair method of linkage analysis and the transmission disequilibrium test (TDT). A subset of 89 affected sibling pairs was genotyped at markers flanking the IL-2 gene as part of a genome-wide search. The IL-2 polymorphism showed no linkage to IBD overall, but modest evidence for linkage to the ulcerative colitis (UC) data set (P = 0.028). A microsatellite 4 cM distal to the IL-2 gene showed a similar distortion in the ulcerative colitis subgroup (P = 0.006). The TDT showed some distortion of allelic transmission for the IL-2 polymorphism in the UC group, but this did not reach statistical significance (P = 0.09). Results for the IL-10 polymorphism were not significant. Thus the gene encoding IL-2 may contribute to UC susceptibility, but the effect is modest and must await replication in other data sets. The IL-10 gene does not appear to contribute to the risk of developing UC or Crohn's disease.