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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
8
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pubmed:dateCreated |
2004-7-30
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pubmed:abstractText |
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.
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1061-4036
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pubmed:author |
pubmed-author:AtkinsonMarkM,
pubmed-author:BachJean-FrancoisJF,
pubmed-author:BruskoToddT,
pubmed-author:DongZhengZ,
pubmed-author:EckenrodeSarahS,
pubmed-author:GarchonHenri-JeanHJ,
pubmed-author:GuoDehuangD,
pubmed-author:HopkinsDianeD,
pubmed-author:JacobChaim OCO,
pubmed-author:LarradMaria T MartinezMT,
pubmed-author:LiManyuM,
pubmed-author:MuirAndrewA,
pubmed-author:ParkYongsooY,
pubmed-author:PodolskyRobert HRH,
pubmed-author:PozzilliPaoloP,
pubmed-author:PurohitSharadS,
pubmed-author:RaffelLeslie JLJ,
pubmed-author:RotterJerome IJI,
pubmed-author:Serrano-RiosManuelM,
pubmed-author:SheJin-XiongJX,
pubmed-author:WangCong-YiCY,
pubmed-author:WangJinzhaoJ,
pubmed-author:YangPingP,
pubmed-author:ZeidlerAdinaA,
pubmed-author:ZhangYanY,
pubmed-author:ZhangZixinZ,
pubmed-author:ZhengWeipengW
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pubmed:issnType |
Print
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pubmed:volume |
36
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
837-41
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:15247916-Amino Acid Sequence,
pubmed-meshheading:15247916-Case-Control Studies,
pubmed-meshheading:15247916-Diabetes Mellitus, Type 1,
pubmed-meshheading:15247916-Gene Expression Regulation,
pubmed-meshheading:15247916-Genetic Predisposition to Disease,
pubmed-meshheading:15247916-Humans,
pubmed-meshheading:15247916-Molecular Sequence Data,
pubmed-meshheading:15247916-Physical Chromosome Mapping,
pubmed-meshheading:15247916-Polymorphism, Single Nucleotide,
pubmed-meshheading:15247916-Sequence Homology, Amino Acid,
pubmed-meshheading:15247916-Small Ubiquitin-Related Modifier Proteins
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pubmed:year |
2004
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pubmed:articleTitle |
A functional variant of SUMO4, a new I kappa B alpha modifier, is associated with type 1 diabetes.
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pubmed:affiliation |
Center for Biotechnology and Genomic Medicine, Medical College of Georgia, 1120 15th Street, CA4098, Augusta, Georgia 30912, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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