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- Dahlqvist, Johanna, 1979-, et al.
(författare)
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Identification and functional characterization of a novel susceptibility locus for small vessel vasculitis with MPO-ANCA
- 2022
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Ingår i: Rheumatology. - Oxford, United Kingdom : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 61:8, s. 3461-3470
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Tidskriftsartikel (refereegranskat)abstract
- Objective To identify and characterize genetic loci associated with the risk of developing ANCA-associated vasculitides (AAV). Methods Genetic association analyses were performed after Illumina sequencing of 1853 genes and subsequent replication with genotyping of selected single nucleotide polymorphisms in a total cohort of 1110 Scandinavian cases with granulomatosis with polyangiitis or microscopic polyangiitis, and 1589 controls. A novel AAV-associated single nucleotide polymorphism was analysed for allele-specific effects on gene expression using luciferase reporter assay. Results PR3-ANCA(+) AAV was significantly associated with two independent loci in the HLA-DPB1/HLA-DPA1 region [rs1042335, P = 6.3 x 10(-61), odds ratio (OR) 0.10; rs9277341, P = 1.5 x 10(-44), OR 0.22] and with rs28929474 in the SERPINA1 gene (P = 2.7 x 10(-10), OR 2.9). MPO-ANCA(+) AAV was significantly associated with the HLA-DQB1/HLA-DQA2 locus (rs9274619, P = 5.4 x 10(-25), OR 3.7) and with a rare variant in the BACH2 gene (rs78275221, P = 7.9 x 10(-7), OR 3.0), the latter a novel susceptibility locus for MPO-ANCA(+) granulomatosis with polyangiitis/microscopic polyangiitis. The rs78275221-A risk allele reduced luciferase gene expression in endothelial cells, specifically, as compared with the non-risk allele. Conclusion We identified a novel susceptibility locus for MPO-ANCA(+) AAV and propose that the associated variant is of mechanistic importance, exerting a regulatory function on gene expression in specific cell types.
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- Ljungman, S., et al.
(författare)
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Factors associated with time to first dialysis-associated peritonitis episode: Data from the Peritonitis Prevention Study (PEPS)
- 2023
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Ingår i: Peritoneal Dialysis International. - 0896-8608. ; 43:3, s. 241-251
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Peritonitis remains a potentially serious complication of peritoneal dialysis (PD) treatment. It is therefore important to identify risk factors in order to reduce the incidence of peritonitis. The aim of the present analysis was to identify factors associated with time to first peritonitis episode. Methods: Incident PD patients from 57 centres in Europe participated in the prospective randomised controlled Peritonitis Prevention Study (PEPS) from 2010 to 2015. Peritonitis-free, self-care PD patients >= 18 years were randomised to a retraining or a control group and followed for 1-36 months after PD initiation. The association of biochemical, clinical and prescription data with time to first peritonitis episode was studied. Results: A first peritonitis episode was experienced by 33% (223/671) of participants. Univariable Cox proportional hazard regression showed a strong association between the time-updated number of PD bags connected per 24 h (PD bags/24 h) and time to first peritonitis episode (HR 1.35; 95% confidence interval (CI) 1.17-1.57), even after inclusion of PD modalities in the same model. Multivariable Cox regression revealed that the factors independently associated with time to first peritonitis episode included age (HR 1.16 per 10 years; 95% CI 1.05-1.28), PD bags/24 h (HR 1.32; 95% CI 1.13-1.54), serum albumin >35 g/L (HR 1.39; 95% CI 1.06-1.82) and body weight per 10 kg (HR 1.10; 95% CI 1.01-1.19). Conclusion: This study of incident PD patients indicates that older age, greater number of PD bags connected/24 h, higher body weight and hypoalbuminaemia are independently associated with a shorter time to first peritonitis episode.
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- Nasic, Salmir, et al.
(författare)
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Sex-specific time trends of long-term graft survival after kidney transplantation - a registry-based study
- 2023
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Ingår i: Renal Failure. - 0886-022X. ; 45:2
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Tidskriftsartikel (refereegranskat)abstract
- Background Sex-specific trends over time with respect to kidney graft survival have scarcely been described in earlier studies. The present study aimed to examine whether kidney graft survival differs between women and men over time.Methods This study was based on prospectively collected data extracted from a quality registry including all kidney transplant patients between January 1965 and September 2017 at the transplantation center of a university hospital in Sweden. The transplantation center serves a population of approximately 3.5 million inhabitants. Only the first graft for each patient was included in the study resulting in 4698 transplantations from unique patients (37% women, 63% men). Patients were followed-up until graft failure, death, or the end of the study. Death-censored graft survival analysis after kidney transplantation (KT) was performed using Kaplan-Meier analysis with log-rank test, and analysis adjusted for confounders was performed using multivariable Cox regression analysis.Results Median age at transplantation was 48 years (quartiles 36-57 years) and was similar for women and men. Graft survival was analyzed separately in four transplantation periods that represented various immunosuppressive regimes (1965-1985, 1986-1995, 1996-2005, and 2006-2017). Sex differences in graft survival varied over time (sex-by-period interaction, p = 0.026). During the three first periods, there were no significant sex differences in graft survival. However, during the last period, women had shorter graft survival (p = 0.022, hazard ratio (HR) 1.71, 95% confidence interval (CI) 1.1-2.7, adjusted for covariates). Biopsy-proven rejections were more common in women.Conclusions In this registry-based study, women had shorter graft survival than men during the last observation period (years 2006-2017).
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