| 1. |
- Shin, J. H., et al.
(författare)
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IA-2 autoantibodies in incident type I diabetes patients are associated with a polyadenylation signal polymorphism in GIMAP5
- 2007
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Ingår i: Genes Immun. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 8:6, s. 503-12
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Tidskriftsartikel (refereegranskat)abstract
- In a large case-control study of Swedish incident type I diabetes patients and controls, 0-34 years of age, we tested the hypothesis that the GIMAP5 gene, a key genetic factor for lymphopenia in spontaneous BioBreeding rat diabetes, is associated with type I diabetes; with islet autoantibodies in incident type I diabetes patients or with age at clinical onset in incident type I diabetes patients. Initial scans of allelic association were followed by more detailed logistic regression modeling that adjusted for known type I diabetes risk factors and potential confounding variables. The single nucleotide polymorphism (SNP) rs6598, located in a polyadenylation signal of GIMAP5, was associated with the presence of significant levels of IA-2 autoantibodies in the type I diabetes patients. Patients with the minor allele A of rs6598 had an increased prevalence of IA-2 autoantibody levels compared to patients without the minor allele (OR=2.2; Bonferroni-corrected P=0.003), after adjusting for age at clinical onset (P=8.0 x 10(-13)) and the numbers of HLA-DQ A1*0501-B1*0201 haplotypes (P=2.4 x 10(-5)) and DQ A1*0301-B1*0302 haplotypes (P=0.002). GIMAP5 polymorphism was not associated with type I diabetes or with GAD65 or insulin autoantibodies, ICA, or age at clinical onset in patients. These data suggest that the GIMAP5 gene is associated with islet autoimmunity in type I diabetes and add to recent findings implicating the same SNP in another autoimmune disease.
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| 2. |
- Sedimbi, S. K., et al.
(författare)
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SUMO4 M55V polymorphism affects susceptibility to type I diabetes in HLA DR3- and DR4-positive Swedish patients
- 2007
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Ingår i: Genes Immun. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 8:6, s. 518-21
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Tidskriftsartikel (refereegranskat)abstract
- SUMO4 M55V, located in IDDM5, has been a focus for debate because of its association to type I diabetes (TIDM) in Asians but not in Caucasians. The current study aims to test the significance of M55V association to TIDM in a large cohort of Swedish Caucasians, and to test whether M55V is associated in those carrying human leukocyte antigen (HLA) class II molecules. A total of 673 TIDM patients and 535 age- and sex-matched healthy controls were included in the study. PCR-RFLP was performed to identify the genotype and allele variations. Our data suggest that SUMO4 M55V is not associated with susceptibility to TIDM by itself. When we stratified our patients and controls based on heterozygosity for HLA-DR3/DR4 and SUMO4 genotypes, we found that presence of SUMO4 GG increased further the relative risk conferred by HLA-DR3/DR4 to TIDM, whereas SUMO4 AA decreased the risk. From the current study, we conclude that SUMO4 M55V is associated with TIDM in association with high-risk HLA-DR3 and DR4, but not by itself.
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| 3. |
- Hampe, C. S., et al.
(författare)
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Reduced display of conformational epitopes in the N-terminal truncated GAD65 isoform : relevance for people with stiff person syndrome or DQ8/8-positive Type 1 diabetes mellitus
- 2019
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Ingår i: Diabetic Medicine. - : Wiley-Blackwell. - 0742-3071 .- 1464-5491. ; 36:11, s. 1375-1383
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To investigate whether the N‐terminal truncated glutamic acid decarboxylase 65 (GAD65) isoform is as well recognized by people with stiff person syndrome as it is by people with Type 1 diabetes, and whether conformational GAD65 antibody epitopes are displayed properly by the isoform.Methods: GAD65 antibody‐positive healthy individuals (n=13), people with stiff‐person syndrome (n=15) and children with new‐onset Type 1 diabetes (n=654) were analysed to determine binding to full‐length GAD65 and the N‐terminal truncated GAD65 isoform in each of these settings. GAD65 autoantibody epitope specificity was correlated with binding ratios of full‐length GAD65/N‐terminal truncated GAD65.Results: The N‐terminal truncated GAD65 isoform was significantly less recognized in GAD65Ab‐positive people with stiff‐person syndrome (P=0.002) and in healthy individuals (P=0.0001) than in people with Type 1 diabetes. Moreover, at least two specific conformational GAD65Ab epitopes were not, or were only partially, presented by the N‐terminal truncated GAD65 isoform compared to full‐length GAD65. Finally, an N‐terminal conformational GAD65Ab epitope was significantly less recognized in DQ8/8 positive individuals with Type 1 diabetes (P=0.02).Conclusions: In people with stiff person syndrome preferred binding to the full‐length GAD65 isoform over the N‐terminal truncated molecule was observed. This binding characteristic is probably attributable to reduced presentation of two conformational epitopes by the N‐terminal truncated molecule. These findings support the notion of disease‐specific GAD65Ab epitope specificities and emphasize the need to evaluate the applicability of novel assays for different medical conditions.
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