| 1. |
- Brorsson, Caroline, et al.
(författare)
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Correlations between islet autoantibody specificity and the SLC30A8 genotype with HLA-DQB1 and metabolic control in new onset type 1 diabetes
- 2011
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Ingår i: Autoimmunity. - : Informa UK Limited. - 0891-6934 .- 1607-842X. ; 44:2, s. 107-114
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Tidskriftsartikel (refereegranskat)abstract
- We hypothesised that the correlation between autoantibody specificity for the ZnT8 Arg325Trp isoforms and the type 2 diabetes-associated rs13266634 may affect beta-cell function at type 1 diabetes (T ID) onset. To study this, we tested 482 newly diagnosed diabetic probands and 478 healthy siblings from the Danish population-based T1D registry for autoantibodies to ZnT8 (ZnT8A) in addition to GAD65 and IA-2. The prevalence and titres of autoantibodies were correlated with genotypes for rs13266634 and HLA-DQB1, age at diagnosis (AAD) and insulin dose-adjusted HbA1c (IDAA1c), as a proxy for residual beta-cell function. We replicated the correlation between rs13266634 genotypes and specificity for the ZnT8-Argenine (ZnT8R) and ZnT8-Tryptophan (ZnT8W) isoforms previously reported. ZnT8A overlapped substantially with autoantibodies to glutamate decarboxylase 65 (GADA) and IA-2 (IA-2A) and correlated significantly with IA-2A prevalence (p < 2e-16). No effect on IDAA1c was demonstrated for ZnT8A or rs13266634. We found a correlation between ZnT8R positivity and HLA-DQB1*0302 genotypes (p = 0.016), which has not been shown previously. Furthermore, significantly lower ZnT8R and GADA prevalence and titres was found among probands with AAD < 5 years (prevalence: p = 0.004 and p = 0.0001; titres: p = 0.002 and p = 0.001, respectively). The same trend was observed for IA-2A and ZnT8W; however, the difference was non-significant. Our study confirms ZnT8 as a major target for autoantibodies at disease onset in our Danish T1D cohort of children and adolescents, and we have further characterised the relationship between autoantibody specificity for the ZnT8 Arg325Trp epitopes and rs13266634 in relation to established autoantibodies, AAD, measures of beta-cell function and HLA-DQB1 genotypes in T1D.
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| 2. |
- Brorsson, Caroline, et al.
(författare)
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The Type 1 Diabetes - HLA Susceptibility Interactome - Identification of HLA Genotype-Specific Disease Genes for Type 1 Diabetes
- 2010
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: The individual contribution of genes in the HLA region to the risk of developing type 1 diabetes (T1D) is confounded by the high linkage disequilibrium (LD) in this region. Using a novel approach we have combined genetic association data with information on functional protein-protein interactions to elucidate risk independent of LD and to place the genetic association into a functional context. Methodology/Principal Findings: Genetic association data from 2300 single nucleotide polymorphisms (SNPs) in the HLA region was analysed in 2200 T1D family trios divided into six risk groups based on HLA-DRB1 genotypes. The best SNP signal in each gene was mapped to proteins in a human protein interaction network and their significance of clustering in functional network modules was evaluated. The significant network modules identified through this approach differed between the six HLA risk groups, which could be divided into two groups based on carrying the DRB1*0301 or the DRB1*0401 allele. Proteins identified in networks specific for DRB1*0301 carriers were involved in stress response and inflammation whereas in DRB1*0401 carriers the proteins were involved in antigen processing and presentation. Conclusions/Significance: In this study we were able to hypothesise functional differences between individuals with T1D carrying specific DRB1 alleles. The results point at candidate proteins involved in distinct cellular processes that could not only help the understanding of the pathogenesis of T1D, but also the distinction between individuals at different genetic risk for developing T1D.
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| 3. |
- Hemborg Kristiansson, Mia, et al.
(författare)
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Pain, power and patience - A narrative study of general practitioners' relations with chronic pain patients
- 2011
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Ingår i: BMC Family Practice. - : Springer Science and Business Media LLC. - 1471-2296. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chronic pain patients are common in general practice. In this study "chronic pain" is defined as diffuse musculoskeletal pain not due to inflammatory diseases or cancer. Effective patient-physician relations improve treatment results. The relationship between doctors and chronic pain patients is often dysfunctional. Consultation training for physicians and medical students can improve the professional ability to build effective relations, but this demands a thorough understanding of the problems in the relation. Several studies have defined the issues that frequently cause problems, but few have described the process. The aim of this study was to understand and illustrate what GPs' experience in contact with chronic pain patients and what works and does not work in these consultations. Methods: Our theoretical perspective is constructivist, based upon the relativist view that individuals construct realities to understand and navigate the world. Five Swedish General Practitioners (GPs), two male and three female, were interviewed and asked to tell a story about a difficult encounter with a chronic pain patient. Tapes of the interviews were transcribed and analysed using narrative analysis. Three GPs told narratives suited for our analytic tools and these were included in the final results. Results: Each narrative highlights a certain dilemma and a strategy. The dilemmas were: power game; good intentions that fail when a patient is persuaded against her own conviction; persuasion of the unwilling; transferred tiredness; distrust and dissociation from the patient. Professional strategies of listening, encouraging and teamwork were central to handling difficult situations. Conclusions: The narratives show that GP's consultations with chronic pain patients sometimes are characterized by conflicts and difficult situations. They are facilitated by methods such as active listening and teamwork, but still may remain hard to handle. This has not before been studied among Swedish GPs. Narratives based on experience are known to be successful in education and this study suggest how narratives can serve as a training of consultation for medical students, but also in Continuing Professional Development groups for experienced doctors in practice.
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