Functional variants in SUMO4, TAB2, and NFκB and the risk of type 1 diabetes

Kosoy, Roman; Concannon, Patrick

doi:10.1038/sj.gene.6364174

Cited by 39 publications

(22 citation statements)

References 38 publications

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“…Two candidate genes, SUMO4 and MAP3K7IP2, are located in the interval, and both products are suggested to be involved in alteration of NF-B activity (7,10,11). In terms of disease pathogenesis, accumulating lines of evidence indicate involvement of the NF-B pathway in the development of type 1 diabetes in humans (15) and mice (25)(26)(27)(28), further supporting the hypothesis that the SUMO4/MAP3K7IP2 locus is responsible for susceptibility to type 1 diabetes.…”

Section: Discussionmentioning

confidence: 73%

“…To test whether the M55V variant of the SUMO4 gene has a population-wide effect in its association with type 1 diabetes, we performed a meta-analysis of published studies including the present study. From seven articles detected by PubMed search, six sets of data (7,9,(12)(13)(14)(15)21), including the present results, were available. Two sets of data (9,15) were excluded from the meta-analysis because some of the subjects from the Human Biological Data Interchange and the Warren Repository overlapped with those in another large-scale association study (13).…”

Section: Resultsmentioning

confidence: 99%

“…The original report by Guo et al (7) with subjects from diverse ethnic groups and the subsequent study by Park et al (12) in Korean subjects showed that possession of the G allele was significantly associated with increased risk for type 1 diabetes, whereas studies in Caucasian subjects of European descent showed no association (13)(14)(15) or even an association of the A allele with the disease (9).…”

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confidence: 99%

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Genetic Heterogeneity in Association of the SUMO4 M55V Variant With Susceptibility to Type 1 Diabetes

Noso

Ikegami²,

Fujisawa³

et al. 2005

Diabetes

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Association studies are a potentially powerful approach to identifying susceptibility variants for common multifactorial diseases such as type 1 diabetes, but the results are not always consistently reproducible. The IDDM5 locus has recently been narrowed to an ϳ200-kb interval on chromosome 6q25 by two independent groups. These studies demonstrated that alleles at markers in the mitogen-activating protein kinase 7 interacting protein 2 (MAP3K7IP2)/ SUMO4 region were associated with susceptibility to type 1 diabetes. Subsequent studies, however, showed inconsistency in the association of the SUMO4 gene with type 1 diabetes. To clarify the contribution of the M55V polymorphism of the SUMO4 gene to type 1 diabetes susceptibility, 541 type 1 diabetic patients and 768 control subjects were studied in Asian populations. T ype 1 diabetes is a common multifactorial disease caused by the autoimmune destruction of insulin-producing ␤-cells of the pancreas. Previous studies have suggested that Ͼ20 genetic intervals are associated with susceptibility to type 1 diabetes (1,2). Of these, four loci have been identified and replicated as disease susceptibility genes by genetic association studies: the HLA class II genes (IDDM1) (3), INS gene (IDDM2) (4), CTLA4 gene (IDDM12) (5), and PTPN22 gene (6). Recently, the IDDM5 locus has been narrowed down to an ϳ200-kb interval on chromosome 6q25 by two independent groups (7,8). Several single nucleotide polymorphisms (SNPs) that were in linkage disequilibrium in the SUMO4/mitogen-activating protein kinase 7 interacting protein 2 (MAP3K7IP2) region were found to be associated with susceptibility to type 1 diabetes (7,9). The SUMO4 gene, encoding small ubiquitin-like modifier 4, is a posttranslational modifier, which has recently been identified as a novel member of the SUMO family and is suggested to modify immune response through the putative substrate, inhibitor of nuclear factor-B␣, a suppressor of nuclear factor-B (NF-B) (7). SUMO4 is located entirely within the sixth intron of the MAP3K7IP2 gene (Fig. 1), whose product indirectly regulates the activation of NF-B in response to interleukin-1 stimulation (10,11).Among the disease-associated SNPs in the SUMO4/ MAP3K7IP2 gene, a common nonsynonymous SNP (rs237025) encoding a methionine-to-valine substitution at codon 55 (M55V) of SUMO4 was proposed as the causative variant of IDDM5 by two groups but with alleles with opposite risk (7,9). The original report by Guo et al. (7) with subjects from diverse ethnic groups and the subsequent study by Park et al. (12) in Korean subjects showed that possession of the G allele was significantly associated with increased risk for type 1 diabetes, whereas studies in Caucasian subjects of European descent showed no association (13-15) or even an association of the A allele with the disease (9).Of note is the positive association in studies with subjects from Asian populations (7,12) in contrast to the lack of association in subjects of European descent (13,14) and a tendency for an opposite assoc...

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Section: Discussionmentioning

confidence: 73%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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Genetic Heterogeneity in Association of the SUMO4 M55V Variant With Susceptibility to Type 1 Diabetes

Noso

Ikegami²,

Fujisawa³

et al. 2005

Diabetes

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“…[16][17][18] However, one study reported an epistatic interaction between NFKB1 and Fc receptor-like 3 (FCRL3) gene in Spanish-Caucasian patients with rheumatoid arthritis. 19 Interestingly, FCRL3 has been recently associated with susceptibility to GD.…”

Section: Nfkb1 Promoter Polymorphism In Graves' Disease a Kurylowicz mentioning

confidence: 99%

Association of NFKB1 −94ins/del ATTG promoter polymorphism with susceptibility to and phenotype of Graves' disease

et al. 2007

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Recently, a functional polymorphism in the NFKB1 gene promoter (À94ins/del ATTG) has been identified and associated with chronic inflammatory diseases. The aim of this study was to analyze the association of NFKB1 polymorphism with susceptibility to and phenotype of Graves' disease (GD). The initial case-control association study, performed in a Polish-Warsaw cohort (388 GD patients and 688 controls), was followed by the two replication studies performed in Polish-Gliwice and JapaneseKurume cohorts (198 GD patients and 194 controls, and 424 GD patients and 222 controls, respectively). The frequency of the À94del ATTG (D) allele was increased in GD compared to controls in Warsaw cohort. This finding was replicated in Gliwice cohort. Combining both Polish-Caucasian cohorts showed that the NFKB1 polymorphism was significantly associated with susceptibility to GD with a codominant mode of inheritance (P ¼ 0.00005; OR ¼ 1.37 (1.18-1.60)). No association with GD was found in Japanese cohort. However, subgroup analysis in Japanese GD patients revealed a correlation between the NFKB1genotype and the development of ophthalmopathy (P ¼ 0.009; OR ¼ 1.49 (1.10-2.01)), and the age of disease onset (P ¼ 0.009; OR ¼ 1.45 (1.09-1.91)). Our results suggest that NFKB1 À94ins/del ATTG polymorphism may be associated with susceptibility to and/or phenotype of GD.

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“…There is a growing amount of evidence that variations within the NFKB1 and NFKBIA genes potentially influence the function of NFKB during development of common inflammatory and autoimmune diseases both in health and various disease conditions such as ulcerative colitis [8,53], Crohn's disease [54], RA, SLE [55], psoriatic arthritis [56], giant cell arteritis [57], Celiac disease [58], Type 1 diabetes [59], oral submucous fibrosis [60], and oral squamous cell carcinoma [60].…”

Section: The Role Of Nfkb1 and Parp-1 Inflammatory Diseasementioning

confidence: 99%

A General Sight about Linking PARP-1 and NFKB1 Variations to the Inflammatory Events

Gk¹,

Yenmiş²,

Koc³

2014

Interdiscip J Microinflammation

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Poly (ADP-ribose) polymerase-1 (PARP-1) has various roles in cellular processes such as DNA repair, genomic stability, transcription, stress response, and cell death via regulating death and inflammation signalling pathways. On the other hand, PARP-1 inhibition has been shown to provide benefits in experimental models of animals with inflammatory diseases such as asthma, atherosclerosis and diabetes. PARP-1 also acts a transcriptional coactivator of nuclear factor kappa B (NFKB). The NFKB is a ubiquitous transcription factor that controls the expression of genes encoding cell adhesion molecules, growth factors, cytokines, and some acute phase proteins. Inappropriate activation of NFKB has been mostly searched with inflammatory events. In complete and persistent inhibition studies of NFKB, apoptosis, inappropriate immune cell development and delayed cell growth were investigated. These findings might provide new perceptions in the pathogenesis of inflammatory disorders regarding the roles of PARP-1 and NFKB1 proteins. In this review, we focus on some variations (rs28362491, rs696, rs1136410, rs2793378, rs7527192) of PARP-1 and NFKB1 genes in relation to susceptibility to common inflammatory diseases including rheumatoid arthritis, systemic lupus erythematosus, allergic rhinitis, Graves' disease, Hashimoto's thyroiditis, asthma and Behcet's disease.

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Functional variants in SUMO4, TAB2, and NFκB and the risk of type 1 diabetes

Cited by 39 publications

References 38 publications

Genetic Heterogeneity in Association of the SUMO4 M55V Variant With Susceptibility to Type 1 Diabetes

Genetic Heterogeneity in Association of the SUMO4 M55V Variant With Susceptibility to Type 1 Diabetes

Association of NFKB1 −94ins/del ATTG promoter polymorphism with susceptibility to and phenotype of Graves' disease

A General Sight about Linking PARP-1 and NFKB1 Variations to the Inflammatory Events

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