Abstract
Interleukin-6 (IL-6) is a pleiotropic cytokine crucial in both adaptive and innate immunity. Numerous genetic studies have shown association with variants of this gene in a multitude of diseases and phenotypes. Most tests of association have focused on a limited set of promoter polymorphisms, in particular, the −174G>C; however, there are many inconsistencies within and between these studies. We propose that there is a more complex regulatory haplotype extending further upstream of the previously characterised promoter region which will provide a more detailed view of the effect of variation on lL-6 regulation. We have exploited two additional single nucleotide polymorphisms (SNPs) in IL-6 that, when examined as a haplotype with existing markers, show an increased level of association with systemic onset juvenile arthritis in a family-based study. This suggests that the haplotype effect may be more functionally relevant to the disease.
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Acknowledgements
This work was supported by the Arthritis Research Campaign. SH and DK are funded by the British Heart Foundation (PG2000/15). We acknowledge the support of the London IDEAS Genetics Knowledge Park.
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Fife, M., Ogilvie, E., Kelberman, D. et al. Novel IL-6 haplotypes and disease association. Genes Immun 6, 367–370 (2005). https://doi.org/10.1038/sj.gene.6364186
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DOI: https://doi.org/10.1038/sj.gene.6364186
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