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

Guo DH; Li MY; Zhang Y; Yang P; Eckenrode S; Hopkins D; Zheng WP; Purohit S; Podolsky RH; Muir A

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

机译：SUMO4的功能性变异体，一种新的IκB alpha修饰剂，与1型糖尿病有关

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Previous studies have suggested more than 20 genetic intervals that are associated with susceptibility to type 1 diabetes (T1D)(1,2), 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 IkappaBalpha and negatively regulates NFkappaB transcriptional activity. The M55V substitution resulted in 5.5 times greater NFkappaB transcriptional activity and similar to2 times greater expression of IL12B, an NFkappaB-dependent gene. These findings suggest a new pathway that may be implicated in the pathogenesis of T1D.

机译：先前的研究表明，与1型糖尿病（T1D）（1,2）的易感性相关的遗传间隔超过20个，但是特定基因的鉴定一直具有挑战性，并且很大程度上局限于已知的候选基因。在这里，我们报告T1D和IDDM5区间中197 kb的基因组DNA中的多个单核苷酸多态性之间存在关联的证据。我们在此间隔内克隆了一个新基因（SUMO4），该基因编码小的泛素样修饰物4蛋白。 SUMO4的关键CUE域的进化保守残基上的取代（M55V）与T1D密切相关（P = 1.9 x 10（-7））。 SUMO4与IkappaBalpha结合，并负调节NFkappaB的转录活性。 M55V取代导致NFkappaB转录活性提高5.5倍，而NFkappaB依赖基因IL12B的表达则提高2倍。这些发现提示可能与T1D的发病机制有关的新途径。

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《Nature Genetics》 |2004年第8期|共5页
作者
Guo DH; Li MY; Zhang Y; Yang P; Eckenrode S; Hopkins D; Zheng WP; Purohit S; Podolsky RH; Muir A;
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正文语种 eng
中图分类医学遗传学;
关键词
CHROMOSOME 11Q13; LINKAGE-DISEQUILIBRIUM; SUSCEPTIBILITY LOCUS; SIGNAL-TRANSDUCTION; ACTIVATION; GENES; MELLITUS; IDDM4; TAB2; RECEPTOR;

机译：染色体11Q13;连锁不平衡;易位性;信号传递;激活;基因;构想;IDDM4;TAB2;受体;

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1. A functional variant of SUMO4, a new I kappa B alpha modifier, is associated with type 1 diabetes [J] . Guo DH, Li MY, Zhang Y, Nature Genetics . 2004,第8期

机译：SUMO4的功能性变异体，一种新的IκB alpha修饰剂，与1型糖尿病有关
2. Polymorphism M55V in gene encoding small ubiquitin-like modifier 4 (SUMO4) protein associates with susceptibility to type 1 (and type 2) diabetes [J] . TangS.-T., PengW.-J., WangC.-J., Diabetes/metabolism research and reviews . 2012,第8期

机译：编码小泛素样修饰物4（SUMO4）蛋白的基因中的多态性M55V与1型（和2型）糖尿病的易感性有关
3. Small Ubiquitin-Like Modifier 4 (SUMO4) Gene M55V Polymorphism and Type 2 Diabetes Mellitus: A Meta-analysis Including 6,823 Subjects [J] . Yan-yan Li, Hui Wang, Xin-xing Yang, Frontiers in Endocrinology . 2017,第1期

机译：小泛素类似物修饰子4（SUMO4）基因M55V多态性与2型糖尿病：一项包括6,823名受试者的荟萃分析
4. Impact Modification of Polyamide 6,6 resins with Conventional And Metallocene Alpha Olefin Backbone Functionalized Modifiers [C] . N. Dharmarajan, T.C. Yu, G.M. Brown, The International Conference on Polyolefins, Feb 27 - Mar 1, 2000, Houston, TX . 2000

机译：常规和茂金属α-烯烃骨架功能改性剂对聚酰胺6,6树脂的冲击改性
5. Structural features and modifiers of islet amyloid polypeptide: Implications for type II diabetes mellitus. [D] . Bedrood, Sahar. 2009

机译：胰岛淀粉样多肽的结构特征和修饰剂：对II型糖尿病的影响。
6. Small Ubiquitin-Like Modifier 4 (SUMO4) Gene M55V Polymorphism and Type 2 Diabetes Mellitus: A Meta-analysis Including 6,823 Subjects [O] . Yan-yan Li, Hui Wang, Xin-xing Yang, 2010

机译：小泛素样修饰子4（SUMO4）基因M55V多态性和2型糖尿病：荟萃分析，包括6,823名受试者。
7. Corrigendum: A functional variant of SUMO4, a new IκBα modifier, is associated with type 1 diabetes [O] . D Guo, M Li, Y Zhang, 2004

机译：勘误：Sumo4的功能变体，一种新的IκBα改性剂，与1型糖尿病有关
8. Study of Configuration Interactions of Atoms of Several Incomplete Electronic Layers. Application and Identification of kappa alpha Satellites in Light Atoms . Etude de Linteraction de Configurations Dans des Atomes a Plusieurs Couches Electroniques Incompletes. Application a Lidentification des Satellites kappa alpha Dans les Atomes Legers [R] . Sureau, A. 1970

机译：几个不完全电子层原子配置相互作用的研究。 Kappa alpha卫星在光原子中的应用与识别。 Etude de Linteraction de Configurations Dans des atomes a plusieurs Couches Electroniques Incompletes。应用Lidentification des satellites kappa alpha Dans les atomes Legers

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

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