<i>SUMO4</i> M55V Variant Is Associated With Diabetic Nephropathy in Type 2 Diabetes

Lin, Hsing-Yi; Wang, Chiao-Ling; Hsiao, Pi‐Jung; Lu, Yung‐Chuan; Chen, Su-Yu; Lin, Kun‐Der; Hsin, Shih-Chie; Hsieh, Ming‐Chia; Shin, Shyi–Jang

doi:10.2337/db06-1283

Cited by 34 publications

(28 citation statements)

References 25 publications

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“…This mutation was strongly correlated with the susceptibility to T1DM, especially in Asian patients and those of European descent in the USA [164,165]. Another study has linked the M55V mutant to the nephropathy associated with type 2 diabetes [166]. SUMO-4 seems to play a role in sumoylating and stabilizing IkBa leading to inactivation of NFkB.…”

Section: Neurodegenerative Diseasesmentioning

confidence: 96%

Sumoylation regulates diverse biological processes

Zhao

2007

Cell. Mol. Life Sci.

212

186

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Ten years after its discovery, the small ubiquitin-like protein modifier (SUMO) has emerged as a key regulator of proteins. While early studies indicated that sumoylation takes place mainly in the nucleus, an increasing number of non-nuclear substrates have recently been identified, suggesting a wider stage for sumoylation in the cell. Unlike ubiquitylation, which primarily targets a substrate for degradation, sumoylation regulates a substrate's functions mainly by altering the intracellular localization, protein-protein interactions or other types of post-translational modifications. These changes in turn affect gene expression, genomic and chromosomal stability and integrity, and signal transduction. Sumoylation is counter-balanced by desumoylation, and well-balanced sumoylation is essential for normal cellular behaviors. Loss of the balance has been associated with a number of diseases. This paper reviews recent progress in the study of SUMO pathways, substrates, and cellular functions and highlights important findings that have accelerated advances in this study field and link sumoylation to human diseases.

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Section: Neurodegenerative Diseasesmentioning

confidence: 96%

Sumoylation regulates diverse biological processes

Zhao

2007

Cell. Mol. Life Sci.

212

186

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“…One of the loci identified as diabetic nephropathy susceptibility genes, 18q22.3, is located near the type 1 diabetes susceptibility loci (IDDM6). Among the genetic variants listed in table 3, ICAM-1 gene, VEGF gene, MBL2 gene, SUMO4 gene, TNF- α gene, TGF- β gene, and MCP-1 gene have been reported as common genetic determinants for the development of both type 1 diabetes and diabetic nephropathy [83,84,85,86,87]. …”

Section: Correlation Of Pathogenesis Between Type 1 Diabetes and Diabmentioning

confidence: 99%

Recent Advancement of Understanding Pathogenesis of Type 1 Diabetes and Potential Relevance to Diabetic Nephropathy

Ichinose

Kawasaki²,

Eguchi³

2007

Am J Nephrol

103

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Type 1 diabetes mellitus is an autoimmune disease characterized by progressive destruction of pancreatic beta cells by genetic and environmental factors which leads to an absolute dependence of insulin for survival and maintenance of health. Although the majority of mechanisms of beta cell destruction remain unclear, many molecules, including proinflammatory cytokines and chemokines such as tumor necrosis factor alpha and monocyte chemoattractant protein-1, are implicated in the development of beta cell damage. Furthermore, beta cell destruction is enhanced by the Th1 and Th17 subsets of CD4+ T cells. In contrast, there are mechanisms involved in the maintenance of peripheral tolerance by regulatory T cells, the function of which depends on the pleiotropic cytokine transforming growth factor beta. Development and progression of renal injuries in patients with diabetic nephropathy are also associated with several growth factors and proinflammatory cytokines, including tumor necrosis factor alpha, insulin-like growth factor-1, monocyte chemoattractant protein-1, vascular endothelial growth factor, and transforming growth factor beta. Although the pathogenic mechanisms underlying type 1 diabetes and diabetic nephropathy are principally different, i.e., autoimmunity and inflammation, some common factors, including susceptibility genes and proinflammatory cytokines, are involved in both mechanisms, including infiltrating cell recruitment, upregulation of other cytokines and chemokines, or apoptosis.

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“…In T2DM subjects, increased glycosaminoglycans (GAG) excretion has been detected (Juretic et al 2002). The MAP3K7IP2 protein is involved in nuclear factor (NF)-κB regulation (Takaesu et al 2000), and SNP rs237025 (M55V) in MAP3K7IP2 has been shown to be associated with T2DM and diabetic nephropathy (Lin et al 2007;Noso et al 2007). SNPs rs12197043 and rs4897081 are approximately 270kb from rs237025.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of a SNP map of 6q24–27 confirms diabetic nephropathy loci and identifies novel associations in type 2 diabetes patients with nephropathy from an African-American population

et al. 2008

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Previously we performed a genome scan for type 2 diabetes (T2DM) using 638 African-American (AA) affected sibling pairs from 247 families; non-parametric linkage analysis suggested evidence of linkage at 6q24-27 (LOD 2.26). To comprehensively evaluate this region we performed a 2-stage association study by first constructing a SNP map of 754 SNPs selected from HapMap on the basis of linkage disequilibrium (LD) in 300 AAT2DM-ESRD subjects, 311 AA controls, 43 European American controls and 45 Yoruba Nigerian samples (Set 1). Replication analyses were conducted in an independent population of 283 AA T2DM-ESRD subjects and 282 AA controls (Set 2). In addition, we adjusted for the impact of admixture on association results by using ancestry informative markers (AIMs). In Stage 1, 137 (18.2%) SNPs showed nominal evidence of association (P<0.05) in one or more of tests of association: allelic (n=33), dominant (n=36), additive (n=29), or recessive (n=34) genotypic models, and 2-(n=47) and 3-SNP (n=43) haplotypic analyses. These SNPs were selected for follow-up genotyping. Stage 2 analyses confirmed association with a predicted 2-SNP "risk" haplotype in the PARK2 gene. Also, two intergenic SNPs showed consistent genotypic association with T2DM-ESRD: rs12197043 and rs4897081. Combined analysis of all subjects from both stages revealed nominal associations with 17 SNPs within genes; including suggestive associations in ESR1 and PARK2. This study confirms known diabetic nephropathy loci and identifies potentially novel susceptibility variants located within 6q24-27 in AA.

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SUMO4 M55V Variant Is Associated With Diabetic Nephropathy in Type 2 Diabetes

Cited by 34 publications

References 25 publications

Sumoylation regulates diverse biological processes

Sumoylation regulates diverse biological processes

Recent Advancement of Understanding Pathogenesis of Type 1 Diabetes and Potential Relevance to Diabetic Nephropathy

Evaluation of a SNP map of 6q24–27 confirms diabetic nephropathy loci and identifies novel associations in type 2 diabetes patients with nephropathy from an African-American population

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