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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

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A functional variant of SUMO4, a new I kappa B alpha modifier, is associated with type 1 diabetes.

Previous studies have suggested more than 20 genetic intervals that are associated with susceptibility to type 1 diabetes (T1D), but identification of specific genes has been challenging and largely limited to known candidate genes. Here, we report evidence for an association between T1D and multiple single-nucleotide polymorphisms in 197 kb of genomic DNA in the IDDM5 interval. We cloned a new gene (SUMO4), encoding small ubiquitin-like modifier 4 protein, in the interval. A substitution (M55V) at an evolutionarily conserved residue of the crucial CUE domain of SUMO4 was strongly associated with T1D (P = 1.9 x 10(-7)). SUMO4 conjugates to I kappa B alpha and negatively regulates NF kappa B transcriptional activity. The M55V substitution resulted in 5.5 times greater NF kappa B transcriptional activity and approximately 2 times greater expression of IL12B, an NF kappa B-dependent gene. These findings suggest a new pathway that may be implicated in the pathogenesis of T1D.[1]

References

  1. A functional variant of SUMO4, a new I kappa B alpha modifier, is associated with type 1 diabetes. Guo, D., Li, M., Zhang, Y., Yang, P., Eckenrode, S., Hopkins, D., Zheng, W., Purohit, S., Podolsky, R.H., Muir, A., Wang, J., Dong, Z., Brusko, T., Atkinson, M., Pozzilli, P., Zeidler, A., Raffel, L.J., Jacob, C.O., Park, Y., Serrano-Rios, M., Larrad, M.T., Zhang, Z., Garchon, H.J., Bach, J.F., Rotter, J.I., She, J.X., Wang, C.Y. Nat. Genet. (2004) [Pubmed]
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