Assessing the validity of the association between the SUMO4 M55V variant and risk of type 1 diabetes

Park, Yong Soo; Park, Sukyung; Kang, Jun-Gu; Yang, Sangsun; Kim, Duk-Hee

doi:10.1038/ng0205-112a

Cited by 46 publications

(39 citation statements)

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“…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 association in British subjects (7,9). Genetic heterogeneity as well as gene-gene and gene-environment interactions have been suggested as possible reasons for these discrepancies observed among different populations.…”

mentioning

confidence: 57%

“…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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confidence: 57%

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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“…Furthermore, in the data reported by Guo et al (2004), there was a subset of 92 multiplex British families featuring a positive, but not significant, association of the 163A allele with disease [61]. Subsequently, some very large studies have failed to find an association [62], while others confirmed the association between SUMO4 M55V polymorphism and T1D [63]. 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.…”

Section: Sumo4mentioning

confidence: 73%

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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“…A non-synonymous coding SNP in the SUMO4 gene within IDDM5 on chromosome 6q25 encodes a methionine to valine substitution at codon 55, which is also associated with T1D [68][69][70]. The intronless gene SUMO4 belongs to the family of small ubiquitin-like modifiers (SUMO family) encoding post-translational modifying proteins [71].…”

Section: Sumo4mentioning

confidence: 99%

Genes Mediating Environment Interactions in Type 1 Diabetes

Biroš

Jordan²,

Baxter

2005

Rev Diabetic Stud

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■ AbstractThe relative risk of type 1 (autoimmune) diabetes mellitus for a sibling of an affected patient is fifteen times that of the general population, indicating a strong genetic contribution to the disease. Yet, the incidence of diabetes in most Western communities has doubled every fifteen years since the Second World War -a rate of increase that can only possibly be explained by a major etiological effect of environment.Here, the authors provide a selective review of risk factors identified to date. Recent reports of linkage of type 1 diabetes to genes encoding pathogen pattern recognition molecules, such as toll-like receptors, are discussed, providing a testable hypothesis regarding a mechanism by which genetic and environmental influences on disease progress are integrated.

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Assessing the validity of the association between the SUMO4 M55V variant and risk of type 1 diabetes

Cited by 46 publications

References 4 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

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

Genes Mediating Environment Interactions in Type 1 Diabetes

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