A functional variant of SUMO4, a new I kappa B alpha modifier, is associated with type 1 diabetes
- PMID: 15247916
- DOI: 10.1038/ng1391
A functional variant of SUMO4, a new I kappa B alpha modifier, is associated with type 1 diabetes
Erratum in
- Nat Genet. 2004 Sep;36(9):1024
Abstract
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.
Comment in
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Assessing the validity of the association between the SUMO4 M55V variant and risk of type 1 diabetes.Nat Genet. 2005 Feb;37(2):110-1; author reply 112-3. doi: 10.1038/ng0205-110. Nat Genet. 2005. PMID: 15678134 No abstract available.
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Assessing the validity of the association between the SUMO4 M55V variant and risk of type 1 diabetes.Nat Genet. 2005 Feb;37(2):111-2; author reply 112-3. doi: 10.1038/ng0205-111. Nat Genet. 2005. PMID: 15678135 No abstract available.
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Assessing the validity of the association between the SUMO4 M55V variant and risk of type 1 diabetes.Nat Genet. 2005 Feb;37(2):112; author reply 112-3. doi: 10.1038/ng0205-112a. Nat Genet. 2005. PMID: 15678137 No abstract available.
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