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- Ombrello, MJ, et al.
(författare)
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Genetic architecture distinguishes systemic juvenile idiopathic arthritis from other forms of juvenile idiopathic arthritis: clinical and therapeutic implications
- 2017
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 76:5, s. 906-913
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Tidskriftsartikel (refereegranskat)abstract
- Juvenile idiopathic arthritis (JIA) is a heterogeneous group of conditions unified by the presence of chronic childhood arthritis without an identifiable cause. Systemic JIA (sJIA) is a rare form of JIA characterised by systemic inflammation. sJIA is distinguished from other forms of JIA by unique clinical features and treatment responses that are similar to autoinflammatory diseases. However, approximately half of children with sJIA develop destructive, long-standing arthritis that appears similar to other forms of JIA. Using genomic approaches, we sought to gain novel insights into the pathophysiology of sJIA and its relationship with other forms of JIA.MethodsWe performed a genome-wide association study of 770 children with sJIA collected in nine countries by the International Childhood Arthritis Genetics Consortium. Single nucleotide polymorphisms were tested for association with sJIA. Weighted genetic risk scores were used to compare the genetic architecture of sJIA with other JIA subtypes.ResultsThe major histocompatibility complex locus and a locus on chromosome 1 each showed association with sJIA exceeding the threshold for genome-wide significance, while 23 other novel loci were suggestive of association with sJIA. Using a combination of genetic and statistical approaches, we found no evidence of shared genetic architecture between sJIA and other common JIA subtypes.ConclusionsThe lack of shared genetic risk factors between sJIA and other JIA subtypes supports the hypothesis that sJIA is a unique disease process and argues for a different classification framework. Research to improve sJIA therapy should target its unique genetics and specific pathophysiological pathways.
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- Hinks, A, et al.
(författare)
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Fine-mapping the MHC locus in juvenile idiopathic arthritis (JIA) reveals genetic heterogeneity corresponding to distinct adult inflammatory arthritic diseases
- 2017
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 76:4, s. 765-772
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Tidskriftsartikel (refereegranskat)abstract
- Juvenile idiopathic arthritis (JIA) is a heterogeneous group of diseases, comprising seven categories. Genetic data could potentially be used to help redefine JIA categories and improve the current classification system. The human leucocyte antigen (HLA) region is strongly associated with JIA. Fine-mapping of the region was performed to look for similarities and differences in HLA associations between the JIA categories and define correspondences with adult inflammatory arthritides.MethodsDense genotype data from the HLA region, from the Immunochip array for 5043 JIA cases and 14 390 controls, were used to impute single-nucleotide polymorphisms, HLA classical alleles and amino acids. Bivariate analysis was performed to investigate genetic correlation between the JIA categories. Conditional analysis was used to identify additional effects within the region. Comparison of the findings with those in adult inflammatory arthritic diseases was performed.ResultsWe identified category-specific associations and have demonstrated for the first time that rheumatoid factor (RF)-negative polyarticular JIA and oligoarticular JIA are genetically similar in their HLA associations. We also observe that each JIA category potentially has an adult counterpart. The RF-positive polyarthritis association at HLA-DRB1 amino acid at position 13 mirrors the association in adult seropositive rheumatoid arthritis (RA). Interestingly, the combined oligoarthritis and RF-negative polyarthritis dataset shares the same association with adult seronegative RA.ConclusionsThe findings suggest the value of using genetic data in helping to classify the categories of this heterogeneous disease. Mapping JIA categories to adult counterparts could enable shared knowledge of disease pathogenesis and aetiology and facilitate transition from paediatric to adult services.
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- Prahalad, P., et al.
(författare)
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Hemoglobin A1c trajectories in the first 18 months after diabetes diagnosis in the SWEET diabetes registry
- 2022
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Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 23:2, s. 228-236
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Tidskriftsartikel (refereegranskat)abstract
- Aim: A majority of youth with type 1 diabetes do not meet recommended hemoglobin A1c (HbA1c) targets. The SWEET diabetes registry is a multi-national registry of youth with diabetes. We used data from this registry to identify characteristics associated with glycemic control. Methods: Patients in the SWEET diabetes registry with at least one HbA1c value within 10 days of diagnosis and three follow up measurements in the first 18 months of diagnosis were included (similar to 10% of the SWEET diabetes registry). Locally weighted scatterplot smoothing was used to generate curves of HbA1c. Wilcoxon, Kruskal-Wallis, chi 2-tests were used to calculate differences between groups. Results: The mean HbA1c of youth in the SWEET diabetes registry is highest at diagnosis and lowest between months 4 and 5 post-diabetes diagnosis. HbA1c continues to increase steadily through the first 18 months of diagnosis. There are no differences in HbA1c trajectories based on sex or use of diabetes technology. Youth in North America/Australia/New Zealand had the highest HbA1c throughout the first 18 months of diagnosis. The trajectory of youth from countries with nationalized health insurance was lower than those countries without nationalized health insurance. Youth from countries with the highest gross domestic product (GDP) had the highest HbA1c throughout the first 18 months of diagnosis. Conclusions: In this subset of patients, the trajectory of youth from countries with nationalized health insurance was lower than those countries without nationalized health insurance. High GDP and high use of technology did not seem to protect from a higher trajectory.
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