Association between the SUMO4 M55V (A163G) polymorphism and susceptibility to type 1 diabetes: A meta-analysis

Song, Gwan Gyu; Choi, Sung Jae; Ji, Jong Dae; Lee, Young Ho

doi:10.1016/j.humimm.2012.07.341

Cited by 9 publications

(7 citation statements)

References 32 publications

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“…Smyth et al (2005) [62] reflected that, given the large numbers of linkage studies performed in T1D, even a small p-value can provide a false positive risk, and that this risk can be compounded by selection biases in the collection of samples, genotyping errors, population substructure, and post-hoc subgroup analyses. At the time of writing, the most recent meta-analysis of SUMO4 polymorphisms in T1D concluded that the SUMO4 M55V polymorphism does confer susceptibility to T1D in Asians, with only a marginal association in Europeans [64].…”

Section: Sumo4mentioning

confidence: 99%

From Markers to Molecular Mechanisms: Type 1 Diabetes in the Post-GWAS Era

Baxter

Jordan²

2012

Rev Diabet Stud

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■ AbstractBy the year 2000, a draft of the human genome sequence was completed. Millions of single-nucleotide polymorphisms (SNPs) had been deposited into public databases, and high throughput technologies were under development for SNP genotyping. At that time, it was predicted that large case control association studies would provide far better resolution and power than genome-wide linkage studies. Type 1 diabetes was one of the first phenotypes to be examined by genome-wide association studies (GWAS), and to date over 50 genomic regions have been associated with the disease.In general, the great majority of these loci individually contribute a relatively small degree of risk, and most loci lie outside of coding sequences. The identification of molecular mechanisms from these genomic data therefore remains a significant challenge. Here, we summarize genetic candidate, linkage, and association studies of type 1 diabetes and discuss a potential strategy to identify mechanisms of disease from genomic data.

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Section: Sumo4mentioning

confidence: 99%

From Markers to Molecular Mechanisms: Type 1 Diabetes in the Post-GWAS Era

Baxter

Jordan²

2012

Rev Diabet Stud

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“…Such negative regulation of the NF κ -B transcription factor hampers transcription of the prosurvival and antiapoptotic proteins [11, 12]. Analysis of several clinical studies on different human populations has enabled an association to be found between multiple polymorphism in and near the gene SUMO4 and susceptibility to diabetes mellitus type 1 [13]. …”

Section: Introductionmentioning

confidence: 99%

Enhanced Apoptosis of Monocytes from Complication-Free Juvenile-Onset Diabetes Mellitus Type 1 May Be Ameliorated by TNF-αInhibitors

Myśliwska

Ryba-Stanisławowska

Smardzewski

et al. 2014

Mediators of Inflammation

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Diabetes mellitus type 1 is associated with an enhanced apoptosis of different cells and tissues, accelerating occurrence of diabetic microvascular complications. The aim of our study was to determine spontaneous apoptotic potential of the monocyte subsets in juvenile-onset complication-free diabetes mellitus type 1 and to compare them with the corresponding values of the healthy. Moreover, we wanted to assess effects of TNF-R1 blocking agents and those of general TNF-α blocker (Infliximab) on spontaneous apoptosis of monocytes. Sixty randomly selected DM1 patients (14.5 ± 3.2 years) and 30 healthy (13.5 ± 2.8 years) volunteers were enrolled in the study. Our results indicate that three monocyte subsets are distinguishable in the groups of young diabetic patients and the healthy, similarly to in the blood of adults. DM1 patients were characterized by higher values of apoptotic monocytes than the healthy. The manipulation with drugs inhibiting TNF-R1 expression diminished the pool of CD16+ apoptotic monocytes. Infliximab reduced the apoptotic CD16− cells. In conclusion, diabetes mellitus type 1 is associated with greater apoptosis of three monocyte subsets which may contribute to the development of microvascular complications. TNF-α modifiers appear to ameliorate monocyte apoptosis. They may be useful for controlling excessive monocyte apoptosis in diabetic patients.

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“…In contrast to SUMO1, both SUMO2 and SUMO3 contain a conserved consensus SUMOylation site in their N‐terminal regions, suggesting that both SUMO2 and SUMO3 are capable to form poly‐SUMO chains [Tatham et al, ]. Currently, the biological role of SUMO4 has been associated with immune system and diabetes development [Song et al, ]; however, the biological significance of SUMO4 is still not well understood. Recent proteomic and developmental studies have demonstrated that modifications by SUMO1/2/3 may regulate both unique and redundant biological pathways and processes [Wang et al, ].…”

mentioning

confidence: 99%

The Key Regulator for Language and Speech Development, FOXP2, is a Novel Substrate for SUMOylation

et al. 2015

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Transcription factor forkhead box protein P2 (FOXP2) plays an essential role in the development of language and speech. However, the transcriptional activity of FOXP2 regulated by the post-translational modifications remains unknown. Here we demonstrated that FOXP2 is clearly defined as a SUMO target protein at the cellular levels as FOXP2 is covalently modified by both SUMO1 and SUMO3. Furthermore, SUMOylation of FOXP2 was significantly decreased by SENP2 (a specific SUMOylation protease). We further showed that FOXP2 is selectively SUMOylated in vivo on a phylogenetically conserved lysine 674 but the SUMOylation does not alter subcellular localization and stability of FOXP2. Interestingly, we observed that human etiological FOXP2 R553H mutation robustly reduces its SUMOylation potential as compared to wild-type FOXP2. In addition, the acidic residues downstream the core SUMO motif on FOXP2 are required for its full SUMOylation capacity. Finally, our functional analysis using reporter gene assays showed that SUMOylation may modulate transcriptional activity of FOXP2 in regulating downstream target genes (DISC1, SRPX2 and MiR200c). Altogether, we provide the first evidence that FOXP2 is a substrate for SUMOylation and SUMOylation of FOXP2 plays a functional role in regulating its transcriptional activity.

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Association between the SUMO4 M55V (A163G) polymorphism and susceptibility to type 1 diabetes: A meta-analysis

Cited by 9 publications

References 32 publications

From Markers to Molecular Mechanisms: Type 1 Diabetes in the Post-GWAS Era

From Markers to Molecular Mechanisms: Type 1 Diabetes in the Post-GWAS Era

Enhanced Apoptosis of Monocytes from Complication-Free Juvenile-Onset Diabetes Mellitus Type 1 May Be Ameliorated by TNF-αInhibitors

The Key Regulator for Language and Speech Development, FOXP2, is a Novel Substrate for SUMOylation

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