| 1. |
- Abelson, Anna-Karin, et al.
(författare)
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No evidence of association between genetic variants of the PDCD1 ligands and SLE
- 2007
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Ingår i: Genes and Immunity. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 8:1, s. 69-74
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Tidskriftsartikel (refereegranskat)abstract
- PDCD1, an immunoreceptor involved in peripheral tolerance has previously been shown to be genetically associated with systemic lupus erythematosus (SLE). PDCD1 has two ligands whose genes are located in close proximity on chromosome 9p24. Our attention was drawn to these ligands after finding suggestive linkage to a marker (gata62f03, Z=2.27) located close to their genes in a genome scan of Icelandic families multiplex for SLE. Here, we analyse Swedish trios (N=149) for 23 single nucleotide polymorphisms (SNPs) within the genes of the PDCD1 ligands. Initially, indication of association to eight SNPs was observed, and these SNPs were therefore also analysed in Mexican trios (N=90), as well as independent sets of patients and controls from Sweden (152 patients, 448 controls) and Argentina (288 patients, 288 controls). We do not find support for genetic association to SLE. This is the first genetic study of SLE and the PDCD1 ligands and the lack of association in several cohorts implies that these genes are not major risk factors for SLE.
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| 2. |
- Adamovic, Svetlana, 1965, et al.
(författare)
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Association study of IL2/IL21 and FcgRIIa: significant association with the IL2/IL21 region in Scandinavian coeliac disease families
- 2008
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Ingår i: Genes and immunity. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 9:4, s. 364-367
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Tidskriftsartikel (refereegranskat)abstract
- The first genome-wide association study performed in a UK coeliac disease (CD) case-control cohort revealed association with a linkage disequilibrium block containing the KIAA1109/Tenr/IL2/IL21 genes. Also recently, an association with a non-synonymous polymorphism in Fcitalic gammaRIIa (CD32a) was reported in CD with an unusually strong P-value. We aimed to replicate the reported associations with the single nucleotide polymorphisms rs13119723 A>G and rs6822844 G>T in the KIAA1109/Tenr/IL2/IL21 region and rs1801274 G>A in the Fcitalic gammaRIIa gene in a family sample consisting of 325 Swedish/Norwegian families using the robust transmission disequilibrium test. The family sample used in this study included 100 families with two or more children affected by CD and 225 families with one affected child. We could confirm significant association between the polymorphisms rs13119723 A>G and rs6822844 G>T located in the KIAA1109/Tenr/IL2/IL21 region and CD (P-value 0.001 and 0.002, respectively). However, we found no association with the Fcitalic gammaRIIa rs1801274 G>A polymorphism (P-value=0.3). In conclusion, our results support the KIAA1109/Tenr/IL2/IL21 region as a true CD susceptibility region.
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| 3. |
- Andersson, H., et al.
(författare)
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Transcriptional profiling of the peripheral blood response during tularemia
- 2006
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Ingår i: Genes and Immunity. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 7:6, s. 503-513
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Tidskriftsartikel (refereegranskat)abstract
- Tularemia is a febrile disease caused by the highly contagious bacterium Francisella tularensis. We undertook an analysis of the transcriptional response in peripheral blood during the course of ulceroglandular tularemia by use of Affymetrix microarrays comprising 14,500 genes. Samples were obtained from seven individuals at five occasions during 2 weeks after the first hospital visit and convalescent samples 3 months later. In total, 265 genes were differentially expressed, 95 of which at more than one time point. The differential expression was verified with real-time quantitative polymerase chain reaction for 36 genes (R(2)=0.590). The most prominent changes were noted in samples drawn on days 2-3 and a considerable proportion of the upregulated genes appeared to represent an interferon-gamma-induced response and also a proapoptotic response. Genes involved in the generation of innate and acquired immune responses were found to be downregulated, presumably a pathogen-induced event. A logistic regression analysis revealed that seven genes were good predictors of the early phase of tularemia. This is the first description of the transcriptional host response to ulceroglandular tularemia and the study has identified gene subsets relevant to the pathogenesis of the disease and subsets that may serve as early diagnostic biomarkers.
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| 4. |
- Benson, Mikael, 1954, et al.
(författare)
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A network-based analysis of allergen-challenged CD4+T cells from patients with allergic rhinitis
- 2006
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Ingår i: Genes and Immunity. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 7:6, s. 514-521
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Tidskriftsartikel (refereegranskat)abstract
- We performed a network-based analysis of DNA microarray data from allergen-challenged CD4 + T cells from patients with seasonal allergic rhinitis. Differentially expressed genes were organized into a functionally annotated network using the Ingenuity Knowledge Database, which is based on manual review of more than 200000 publications. The main function of this network is the regulation of lymphocyte apoptosis, a role associated with several genes of the tuber necrosis factor superfamily. The expression of TNFRSF4, one of the genes in this family, was found to be 48 times higher in allergen-challenged cells than in diluent-challenged cells. TNFRSF4 is known to inhibit apoptosis and to enhance Th2 proliferation. Examination of a different material of allergen-stimulated peripheral blood mononuclear cells showed a higher number of interleukin-4 + type 2 CD4 + T (Th2) cells in patients than in controls (P
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| 5. |
- Bergholdt, R., et al.
(författare)
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No association of the IRS1 and PAX4 genes with type I diabetes
- 2009
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Ingår i: Genes and Immunity. - : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 10, s. 49-53
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Tidskriftsartikel (refereegranskat)abstract
- To reassess earlier suggested type I diabetes (T1D) associations of the insulin receptor substrate 1 (IRS1) and the paired domain 4 gene (PAX4) genes, the Type I Diabetes Genetics Consortium (T1DGC) evaluated single-nucleotide polymorphisms (SNPs) covering the two genomic regions. Sixteen SNPs were evaluated for IRS1 and 10 for PAX4. Both genes are biological candidate genes for T1D. Genotyping was performed in 2300 T1D families on both Illumina and Sequenom genotyping platforms. Data quality and concordance between the platforms were assessed for each SNP. Transmission disequilibrium testing neither show T1D association of SNPs in the two genes, nor did haplotype analysis. In conclusion, the earlier suggested associations of IRS1 and PAX4 to T1D were not supported, suggesting that they may have been false positive results. This highlights the importance of thorough quality control, selection of tagging SNPs, more than one genotyping platform in high throughput studies, and sufficient power to draw solid conclusions in genetic studies of human complex diseases. Genes and Immunity (2009) 10, S49-S53; doi:10.1038/gene.2009.91
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| 6. |
- Bergholdt, R, et al.
(författare)
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Transcriptional profiling of type 1 diabetes genes on chromosome 21 in a rat beta-cell line and human pancreatic islets
- 2007
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Ingår i: Genes and Immunity. - : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 8:3, s. 232-238
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Tidskriftsartikel (refereegranskat)abstract
- We recently finemapped a type 1 diabetes (T1D)-linked region on chromosome 21, indicating that one or more T1D-linked genes exist in this region with 33 annotated genes. In the current study, we have taken a novel approach using transcriptional profiling in predicting and prioritizing the most likely candidate genes influencing beta-cell function in this region. Two array-based approaches were used, a rat insulinoma cell line (INS-1 alpha beta) overexpressing pancreatic duodenum homeobox 1 (pdx-1) and treated with interleukin 1 beta (IL-1 beta) as well as human pancreatic islets stimulated with a mixture of cytokines. Several candidate genes with likely functional significance in T1D were identified. Genes showing differential expression in the two approaches were highly similar, supporting the role of these specific gene products in cytokine-induced beta-cell damage. These were genes involved in cytokine signaling, oxidative phosphorylation, defense responses and apoptosis. The analyses, furthermore, revealed several transcription factor binding sites shared by the differentially expressed genes and by genes demonstrating highly similar expression profiles with these genes. Comparable findings in the rat beta-cell line and human islets support the validity of the methods used and support this as a valuable approach for gene mapping and identification of genes with potential functional significance in T1D, within a region of linkage.
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| 10. |
- Delgado-Vega, Angelica M., et al.
(författare)
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Replication of the TNFSF4 (OX40L) promoter region association with systemic lupus erythematosus
- 2009
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Ingår i: Genes and Immunity. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 10:3, s. 248-253
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Tidskriftsartikel (refereegranskat)abstract
- The tumor necrosis factor ligand superfamily member 4 gene (TNFSF4) encodes the OX40 ligand (OX40L), a costimulatory molecule involved in T-cell activation. A recent study demonstrated the association of TNFSF4 haplotypes located in the upstream region with risk for or protection from systemic lupus erythematosus (SLE). To replicate this association, five single nucleotide polymorphisms (SNPs) tagging the previously associated haplotypes and passing the proper quality-control filters were tested in 1312 cases and 1801 controls from Germany, Italy, Spain and Argentina. The association of TNFSF4 with SLE was replicated in all the sets except Spain. There was a unique risk haplotype tagged by the minor alleles of the SNPs rs1234317 (pooled odds ratio (OR)=1.39, P=0.0009) and rs12039904 (pooled OR=1.38, P=0.0012). We did not observe association to a single protective marker (rs844644) or haplotype as the first study reported; instead, we observed different protective haplotypes, all carrying the major alleles of both SNPs rs1234317 and rs12039904. Association analysis conditioning on the haplotypic background confirmed that these two SNPs explain the entire haplotype effect. This first replication study confirms the association of genetic variation in the upstream region of TNFSF4 with susceptibility to SLE.
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