| 1. |
- Gyllenberg, A, et al.
(författare)
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Variability in the CIITA gene interacts with HLA in multiple sclerosis.
- 2014
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Ingår i: Genes and immunity. - Stockholm : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- The human leukocyte antigen (HLA) is the main genetic determinant of multiple sclerosis (MS) risk. Within the HLA, the class II HLA-DRB1*15:01 allele exerts a disease-promoting effect, whereas the class I HLA-A*02 allele is protective. The CIITA gene is crucial for expression of class II HLA molecules and has previously been found to associate with several autoimmune diseases, including MS and type 1 diabetes. We here performed association analyses with CIITA in 2000 MS cases and up to 6900 controls as well as interaction analysis with HLA. We find that the previously investigated single-nucleotide polymorphism rs4774 is associated with MS risk in cases carrying the HLA-DRB1*15 allele (P=0.01, odds ratio (OR): 1.21, 95% confidence interval (CI): 1.04-1.40) or the HLA-A*02 allele (P=0.01, OR: 1.33, 95% CI: 1.07-1.64) and that these associations are independent of the adjacent confirmed MS susceptibility gene CLEC16A. We also confirm interaction between rs4774 and HLA-DRB1*15:01 such that individuals carrying the risk allele for rs4774 and HLA-DRB1*15:01 have a higher than expected risk for MS. In conclusion, our findings support previous data that variability in the CIITA gene affects MS risk, but also that the effect is modulated by MS-associated HLA haplotypes. These findings further underscore the biological importance of HLA for MS risk.Genes and Immunity advance online publication, 16 January 2014; doi:10.1038/gene.2013.71.
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| 2. |
- 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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| 3. |
- Kochar, Bharati, et al.
(författare)
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Prevalence and Implications of Frailty in Older Adults With Incident Inflammatory Bowel Diseases : A Nationwide Cohort Study
- 2022
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Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 20:10, s. 2358-2365
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: We aimed to compare the risk of frailty in older adults with incident inflammatory bowel disease (IBD) and matched non-IBD comparators and assess the association between frailty and future hospitalizations and mortality.Methods: In a cohort of patients with incident IBD ≥60 years of age from 2007 to 2016 in Sweden identified using nationwide registers, we defined frailty using Hospital Frailty Risk Score. We compared prevalence of frailty in patients with IBD with age, sex, place of residency– and calendar year–matched population comparators. In the IBD cohort, we used Cox proportional hazards modeling to examine the associations between frailty risk and hospitalizations or mortality.Results: We identified 10,590 patients with IBD, 52% female with a mean age of 71 years of age, matched to 103,398 population-based comparators. Among patients with IBD, 39% had no risk for frailty, 49% had low risk for frailty, and 12% had higher risk for frailty. Mean Hospital Frailty Risk Score was 1.9 in IBD and 0.9 in matched comparators (P < .01). Older adults with IBD at higher risk for frailty had a 20% greater risk for mortality at 3 years compared with those who were not frail. Compared with nonfrail older patients with IBD, patients at higher risk for frailty had increased mortality (hazard ratio [HR], 3.22, 95% confidence interval [CI], 2.86–3.61), all-cause hospitalization (HR, 2.42; 95% CI, 2.24–2.61), and IBD-related hospitalization (HR, 1.50; 95% CI, 1.35–1.66). These associations were not attenuated after adjusting for comorbidities.Conclusions: Frailty is more prevalent in older adults with IBD than in matched comparators. Among older patients with IBD, frailty is associated with increased risk for hospitalizations and mortality.
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| 4. |
- Humes, D. J., et al.
(författare)
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Risk of symptomatic venous thromboembolism following emergency appendicectomy in adults
- 2016
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Ingår i: British Journal of Surgery. - West, Sussex, United Kingdom : John Wiley & Sons. - 0007-1323 .- 1365-2168. ; 103:4, s. 443-450
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Tidskriftsartikel (refereegranskat)abstract
- Background: Appendicectomy is the commonest intra-abdominal emergency surgical procedure, and little is known regarding the magnitude and timing of the risk of venous thromboembolism (VTE) after surgery. This study aimed to determine absolute and relative rates of symptomatic VTE following emergency appendicectomy.Methods: A cohort study was undertaken using linked primary (Clinical Practice Research Datalink) and secondary (Hospital Episode Statistics) care data of patients who had undergone emergency appendicectomy from 2001 to 2011. Crude rates and adjusted incidence rate ratios (IRRs) for VTE were calculated using Poisson regression, compared with baseline risk in the year before appendicectomy.Results: A total of 13 441 patients were identified, of whom 56 (0·4 per cent) had a VTE in the first year after surgery. The absolute rate of VTE was highest during the in-hospital period, with a rate of 91·29 per 1000 person-years, which was greatest in those with a length of stay of 7 days or more (267·12 per 1000 person-years). This risk remained high after discharge, with a 19·1- and 6·6-fold increased risk of VTE in the first and second months respectively after discharge, compared with the year before appendicectomy (adjusted IRR: month 1, 19·09 (95 per cent c.i. 9·56 to 38·12); month 2, 6·56 (2·62 to 16·44)).Conclusion: The risk of symptomatic VTE following appendicectomy is relatively high during the in-hospital admission and remains increased after discharge. Trials of extended thromboprophylaxis are warranted in patients at particularly high risk.
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| 5. |
- Shrestha, Sarita, 1991-, et al.
(författare)
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The use of ICD codes to identify IBD subtypes and phenotypes of the Montreal classification in the Swedish National Patient Register
- 2020
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 55:4, s. 430-435
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Whether data on International Classification of Diseases (ICD)-codes from the Swedish National Patient Register (NPR) correctly correspond to subtypes of inflammatory bowel disease (IBD) and phenotypes of the Montreal classification scheme among patients with prevalent disease is unknown. Materials and methods: We obtained information on IBD subtypes and phenotypes from the medical records of 1403 patients with known IBD who underwent biological treatment at ten Swedish hospitals and retrieved information on their IBD-associated diagnostic codes from the NPR. We used previously described algorithms to define IBD subtypes and phenotypes. Finally, we compared these register-generated subtypes and phenotypes with the corresponding information from the medical records and calculated positive predictive values (PPV) with 95% confidence intervals. Results: Among patients with clinically confirmed disease and diagnostic listings of IBD in the NPR (N = 1401), the PPV was 97 (96-99)% for Crohn's disease, 98 (97-100)% for ulcerative colitis, and 8 (4-11)% for IBD-unclassified. The overall accuracy for age at diagnosis was 95% (when defined as A1, A2, or A3). Examining the validity of codes representing disease phenotype, the PPV was 36 (32-40)% for colonic Crohn's disease (L2), 61 (56-65)% for non-stricturing/non-penetrating Crohn's disease behaviour (B1) and 83 (78-87)% for perianal disease. Correspondingly, the PPV was 80 (71-89)% for proctitis (E1)/left-sided colitis (E2) in ulcerative colitis. Conclusions: Among people with known IBD, the NPR is a reliable source of data to classify most subtypes of prevalent IBD, even though misclassification commonly occurred in Crohn's disease location and behaviour and also among IBD-unclassified patients.
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| 7. |
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| 8. |
- 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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| 9. |
- Skov, J., et al.
(författare)
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Co-aggregation and heritability of organ-specific autoimmunity: a population-based twin study
- 2020
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 182:5, s. 473-480
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Co-aggregation of autoimmune diseases is common, suggesting pa rtly shared etiologies. Genetic factors are believed to be important, but objective measures of environ mental vs heritable influences on co-aggregation are absent. With a novel approach to twin studies, we aimed at esti mating heritability and genetic overlap in seven organspecific autoimmune diseases. Design: Prospective twin cohort study. Methods: We used a cohort of 110 814 twins to examine co-aggregation an d heritability of Hashimoto's thyroiditis, atrophic gastritis, celiac disease, Graves' disease, type 1 dia betes, vitiligo and Addison's disease. Hazard ratios (HR) were calculated for twins developing the same or different disea se as compared to their co-twin. The differences between monozygotic and dizygotic twin pairs were used to estim ate the genetic influence on co- aggregation. Heritability for individual disorders was calculated using stru ctural equational modeling adjusting for censoring and truncation of data. Results: Co-aggregation was more pronounced in monozygotic twins (media n HR: 3.2, range: 2.2-9.2) than in dizygotic twins (median HR: 2.4, range: 1.1-10.0). Heritability was moder ate for atrophic gastritis (0.38, 95% CI: 0.23-0.53) but high for all other diseases, ranging from 0.60 (95% CI: 0.49-0. 71) for Graves' disease to 0.97 (95% CI: 0.91- 1.00) for Addison's disease. Conclusions: Overall, co-aggregation was more pronounced in monozygotic tha n in dizygotic twins, suggesting that disease overlap is largely attributable to genetic factors. Co- aggregation was common, and twins faced up to a ten-fold risk of developing diseases not present in their co-twin. Our r esults validate and refine previous heritability estimates based on smaller twin cohorts.
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| 10. |
- Bröms, G., et al.
(författare)
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Disease characteristics at time of diagnosis of adult onset inflammatory bowel disease and the risk of venous thromboembolism in the modern era - A Swedish nationwide cohort study 2007-2021
- 2024
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Ingår i: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 18:Suppl. 1, s. I1945-I1947
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Studies from mainly before the wide use of targeted therapies and guidelines for thromboprophylaxis indicate that patients with inflammatory bowel disease (IBD) are at a doubled risk of venous thromboembolism (VTE). We studied the risk of VTE in a modern-day cohort of patients with IBD, overall and in subgroups of disease characteristics.Methods: Using Swedish healthcare registers, we identified a nationwide population-based cohort of 55,252 patients with incident IBD between 2007 and 2021 with a median follow-up time of 6.5 years. Patients were matched by age, sex, calendar year and county of residence with up to ten reference individuals from the general population (N=536,067). The primary outcome was VTE, including pulmonary embolism and deep vein thrombosis. Incidence rates per 1,000 person-years and hazard ratios (HR) were calculated for IBD in general and according to disease subtype, sex, age and disease characteristics at diagnosis. HRs stratified by matching variables (model 1) and additionally adjusted for comorbidities and socioeconomic factors (model 2) were estimated by using Cox regression.Results: The incidence rate of VTE among patients with IBD was 5.03 per 1,000 person-years compared with 2.34 per 1,000 person-years among reference individuals (Table 1). This corresponded to a doubled incidence of VTE (HR=2.18, 95% confidence interval (CI)=2.07-2.29, model 1). Adjusting further for covariates in model 2 had only minor effects on the HR. The HR was consistent across IBD subtypes and sex. The relative risk was higher for those with younger age (18-39 years) at IBD diagnosis (HR 2.52, 95% CI: 2.22-2.83) with a risk difference of 1.25 per 1,000 person-years. The IR, 10.64 per 1,000 person-years, and risk difference, 5.42 per 1,000 person-years, was the highest for those with elderly onset (≥60 years) IBD. There was a stronger association for those with extensive ulcerative colitis (E3), primary sclerosing cholangitis, extraintestinal manifestations and perianal disease. HRs for VTE were persistently elevated across follow-up time, but was higher during the first year of follow-up (Figure 1).Conclusion: The risk of VTE was doubled in these modern-day data and remained elevated across follow-up time. Disease characteristics associated with higher inflammatory burden at diagnosis and older age are markers of increased risk. This underscores the importance of continuous vigilance and individual assessment of risk factors for VTE in patients with IBD.
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