Endocrine Abstracts

Genome wide screens in Graves’ disease (GD) have identified several regions of linkage which may harbour genes which contribute to disease susceptibility. One such region, on chromosome 5q31-33, contains a cytokine cluster which includes interleukin-13 (IL-13). This molecule plays a key role in IgE production, which has been reported to be elevated in patients with GD. Two functional single nucleotide polymorphisms (SNPs), -1112 and +2044, within the IL-13 gene were recently associated with GD in a small Japanese population. However, this result was not replicated in a Polish Caucasian GD population. The aim of this study was to verify the role played by these SNPs in susceptibility to GD using a large UK Caucasian dataset with >90% power to exclude effects of these SNPs. DNA was obtained from 1056 unrelated GD patients and 864 ethnically matched control subjects. All subjects gave informed written consent and the project was approved by the local research ethics committee. Neither the −1112 or the +2044 SNP were found to be associated with GD (P=0.892 and P=0.647, respectively). This could be due to a number of reasons. Firstly, the original study could represent a false positive result due to the small dataset used. Secondly, association of these SNPs could be population specific and thirdly, although elevated IgE levels in GD patients has been reported, it is unknown if elevated IgE is a cause or consequence of GD. In conclusion, this study has found no evidence to suggest that these SNPs are involved in susceptibility to GD in a Caucasian population. However, involvement of the IL-13 gene with GD in such a population cannot be excluded without the use of a fine mapping strategy to identify and genotype all SNPs within this gene.