| 1. |
- Saevarsdottir, S., et al.
(författare)
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Multiomics analysis of rheumatoid arthritis yields sequence variants that have large effects on risk of the seropositive subset
- 2022
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 81:8
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To find causal genes for rheumatoid arthritis (RA) and its seropositive (RF and/or ACPA positive) and seronegative subsets. Methods We performed a genome-wide association study (GWAS) of 31 313 RA cases (68% seropositive) and similar to 1 million controls from Northwestern Europe. We searched for causal genes outside the HLA-locus through effect on coding, mRNA expression in several tissues and/or levels of plasma proteins (SomaScan) and did network analysis (Qiagen). Results We found 25 sequence variants for RA overall, 33 for seropositive and 2 for seronegative RA, altogether 37 sequence variants at 34 non-HLA loci, of which 15 are novel. Genomic, transcriptomic and proteomic analysis of these yielded 25 causal genes in seropositive RA and additional two overall. Most encode proteins in the network of interferon-alpha/beta and IL-12/23 that signal through the JAK/STAT-pathway. Highlighting those with largest effect on seropositive RA, a rare missense variant in STAT4 (rs140675301-A) that is independent of reported non-coding STAT4-variants, increases the risk of seropositive RA 2.27-fold (p=2.1x10(-9)), more than the rs2476601-A missense variant in PTPN22 (OR=1.59, p=1.3x10(-160)). STAT4 rs140675301-A replaces hydrophilic glutamic acid with hydrophobic valine (Glu128Val) in a conserved, surface-exposed loop. A stop-mutation (rs76428106-C) in FLT3 increases seropositive RA risk (OR=1.35, p=6.6x10(-11)). Independent missense variants in TYK2 (rs34536443-C, rs12720356-C, rs35018800-A, latter two novel) associate with decreased risk of seropositive RA (ORs=0.63-0.87, p=10(-9)-10(-27)) and decreased plasma levels of interferon-alpha/beta receptor 1 that signals through TYK2/JAK1/STAT4. Conclusion Sequence variants pointing to causal genes in the JAK/STAT pathway have largest effect on seropositive RA, while associations with seronegative RA remain scarce.
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| 2. |
- Olafsson, S, et al.
(författare)
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Fourteen sequence variants that associate with multiple sclerosis discovered by meta-analysis informed by genetic correlations
- 2017
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Ingår i: NPJ genomic medicine. - : Springer Science and Business Media LLC. - 2056-7944. ; 2, s. 24-
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Tidskriftsartikel (refereegranskat)abstract
- A meta-analysis of publicly available summary statistics on multiple sclerosis combined with three Nordic multiple sclerosis cohorts (21,079 cases, 371,198 controls) revealed seven sequence variants associating with multiple sclerosis, not reported previously. Using polygenic risk scores based on public summary statistics of variants outside the major histocompatibility complex region we quantified genetic overlap between common autoimmune diseases in Icelanders and identified disease clusters characterized by autoantibody presence/absence. As multiple sclerosis-polygenic risk scores captures the risk of primary biliary cirrhosis and vice versa (P = 1.6 × 10−7, 4.3 × 10−9) we used primary biliary cirrhosis as a proxy-phenotype for multiple sclerosis, the idea being that variants conferring risk of primary biliary cirrhosis have a prior probability of conferring risk of multiple sclerosis. We tested 255 variants forming the primary biliary cirrhosis-polygenic risk score and found seven multiple sclerosis-associating variants not correlated with any previously established multiple sclerosis variants. Most of the variants discovered are close to or within immune-related genes. One is a low-frequency missense variant in TYK2, another is a missense variant in MTHFR that reduces the function of the encoded enzyme affecting methionine metabolism, reported to be dysregulated in multiple sclerosis brain.
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| 3. |
- Stacey, Simon N, et al.
(författare)
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A germline variant in the TP53 polyadenylation signal confers cancer susceptibility.
- 2011
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 43:11, s. 1098-103
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Tidskriftsartikel (refereegranskat)abstract
- To identify new risk variants for cutaneous basal cell carcinoma, we performed a genome-wide association study of 16 million SNPs identified through whole-genome sequencing of 457 Icelanders. We imputed genotypes for 41,675 Illumina SNP chip-typed Icelanders and their relatives. In the discovery phase, the strongest signal came from rs78378222[C] (odds ratio (OR) = 2.36, P = 5.2 × 10(-17)), which has a frequency of 0.0192 in the Icelandic population. We then confirmed this association in non-Icelandic samples (OR = 1.75, P = 0.0060; overall OR = 2.16, P = 2.2 × 10(-20)). rs78378222 is in the 3' untranslated region of TP53 and changes the AATAAA polyadenylation signal to AATACA, resulting in impaired 3'-end processing of TP53 mRNA. Investigation of other tumor types identified associations of this SNP with prostate cancer (OR = 1.44, P = 2.4 × 10(-6)), glioma (OR = 2.35, P = 1.0 × 10(-5)) and colorectal adenoma (OR = 1.39, P = 1.6 × 10(-4)). However, we observed no effect for breast cancer, a common Li-Fraumeni syndrome tumor (OR = 1.06, P = 0.57, 95% confidence interval 0.88-1.27).
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| 4. |
- Castor, C, et al.
(författare)
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Psychometric evaluation of the electronic faces thermometer scale for pain assessment in children 8–17 years old : A study protocol
- 2023
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Ingår i: Paediatric and Neonatal Pain. - : John Wiley & Sons. - 2637-3807 .- 2379-5824. ; 5:4, s. 99-109
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Tidskriftsartikel (refereegranskat)abstract
- It is often a challenge for a child to communicate their pain, and their possibilities to do so should be strengthened in healthcare settings. Digital self-assessment provides a potential solution for person-centered care in pain management and promotes child participation when a child is ill. A child's perception of pain assessment differs when it is assessed using digital or analog formats. As we move into the digital era, there is an urgent need to validate digital pain assessment tools, including the newly developed electronic Faces Thermometer Scale (eFTS). This study protocol describes three studies with the overall aim to evaluate psychometric properties of the eFTS for assessing pain in children 8?17?years of age. A multi-site project design combining quantitative and qualitative methods will be used for three observational studies. Study 1: 100 Swedish-speaking children will report the level of anticipated pain from vignettes describing painful situations in four levels of pain and a think-aloud method will be used for data collection. Data will be analyzed with phenomenography as well as descriptive and comparative statistics. Study 2: 600 children aged 8?17?years at pediatric and dental settings in Sweden, Denmark, Iceland, and USA will be included. Children will assess their pain intensity due to medical or dental procedures, surgery, or acute pain using three different pain Scales for each time point; the eFTS, the Faces Pain Scale Revised, and the Coloured Analogue Scale. Descriptive and comparative statistics will be used, with subanalysis taking cultural context into consideration. Study 3: A subgroup of 20 children out of these 600 children will be purposely included in an interview to describe experiences of grading their own pain using the eFTS. Qualitative data will be analyzed with content analysis. Our pilot studies showed high level of adherence to the study procedure and rendered only a small revision of background questionnaires. Preliminary analysis indicated that the instruments are adequate to be used by children and that the analysis plan is feasible. A digital pain assessment tool contributes to an increase in pain assessment in pediatric care. The Medical Research Council framework for complex interventions in healthcare supports a thorough development of a new scale. By evaluating psychometric properties in several settings by both qualitative and quantitative methods, the eFTS will become a well-validated tool to strengthen the child's voice within healthcare.
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| 5. |
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| 6. |
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| 7. |
- Castor, C, et al.
(författare)
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Psychometric evaluation of the electronic faces thermometer scale for pain assessment in children 8–17years old: A study protocol
- 2023
-
Ingår i: Paediatric and Neonatal Pain. - : Wiley. - 2379-5824 .- 2637-3807. ; 5:4, s. 99-109
-
Tidskriftsartikel (refereegranskat)abstract
- It is often a challenge for a child to communicate their pain, and their possibilities to do so should be strengthened in healthcare settings. Digital self-assessment provides a potential solution for person-centered care in pain management and promotes child participation when a child is ill. A child's perception of pain assessment differs when it is assessed using digital or analog formats. As we move into the digital era, there is an urgent need to validate digital pain assessment tools, including the newly developed electronic Faces Thermometer Scale (eFTS). This study protocol describes three studies with the overall aim to evaluate psychometric properties of the eFTS for assessing pain in children 8–17years of age. A multi-site project design combining quantitative and qualitative methods will be used for three observational studies. Study 1: 100 Swedish-speaking children will report the level of anticipated pain from vignettes describing painful situations in four levels of pain and a think-aloud method will be used for data collection. Data will be analyzed with phenomenography as well as descriptive and comparative statistics. Study 2: 600 children aged 8–17years at pediatric and dental settings in Sweden, Denmark, Iceland, and USA will be included. Children will assess their pain intensity due to medical or dental procedures, surgery, or acute pain using three different pain Scales for each time point; the eFTS, the Faces Pain Scale Revised, and the Coloured Analogue Scale. Descriptive and comparative statistics will be used, with subanalysis taking cultural context into consideration. Study 3: A subgroup of 20 children out of these 600 children will be purposely included in an interview to describe experiences of grading their own pain using the eFTS. Qualitative data will be analyzed with content analysis. Our pilot studies showed high level of adherence to the study procedure and rendered only a small revision of background questionnaires. Preliminary analysis indicated that the instruments are adequate to be used by children and that the analysis plan is feasible. A digital pain assessment tool contributes to an increase in pain assessment in pediatric care. The Medical Research Council framework for complex interventions in healthcare supports a thorough development of a new scale. By evaluating psychometric properties in several settings by both qualitative and quantitative methods, the eFTS will become a well-validated tool to strengthen the child's voice within healthcare.
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| 8. |
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| 9. |
- de Rooy, D. P. C., et al.
(författare)
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Smoking as a risk factor for the radiological severity of rheumatoid arthritis: a study on six cohorts
- 2014
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 73:7, s. 1384-1387
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Tidskriftsartikel (refereegranskat)abstract
- Background Smoking is a risk factor for the development of anti -citrullinated protein antibodies (ACPA) positive rheumatoid arthritis (RA). Whether smoking predisposes to severe joint damage progression is not known, since deleterious, protective and neutral observations have been made. Objective To determine the effect of smoking on joint damage progression. Methods Smoking status was assessed in 3158 RA patients included in six cohorts (Leiden Early Arthritis Clinic (Leiden-EAC), BARFOT, Lund, Iceland, NDB and Wichita). In total 9412 radiographs were assessed. Multivariate normal regression and linear regression analyses were performed. Data were summarised in a random effects inverse variance meta-analysis. Results When comparing radiological progression for RA patients that were never, past and current smokers, smoking was significantly associated with more severe joint damage in Leiden-EAC (p=0.042) and BARFOT (p=0.015) RA patients. No significant associations were found in the other cohorts, though a meta-analysis on the six cohorts showed significantly more severe joint damage progression in smokers (p=0.01). Since smoking predisposes to ACPA, analyses were repeated with ACPA as additional adjustment factor. Then the association was lost (meta-analysis p=0.29). Conclusions This multi-cohort study indicated that the effect of smoking on joint damage is mediated via ACPA and that smoking is not an independent risk factor for radiological progression in RA.
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| 10. |
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| 11. |
- Kristjansdottir, Thordis, et al.
(författare)
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Engineering the carotenoid biosynthetic pathway in Rhodothermus marinus for lycopene production
- 2020
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Ingår i: Metabolic Engineering Communications. - : Elsevier BV. - 2214-0301. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Rhodothermus marinus has the potential to be well suited for biorefineries, as an aerobic thermophile that produces thermostable enzymes and is able to utilize polysaccharides from different 2nd and 3rd generation biomass. The bacterium produces valuable chemicals such as carotenoids. However, the native carotenoids are not established for industrial production and R. marinus needs to be genetically modified to produce higher value carotenoids. Here we genetically modified the carotenoid biosynthetic gene cluster resulting in three different mutants, most importantly the lycopene producing mutant TK-3 (ΔtrpBΔpurAΔcruFcrtB::trpBcrtBT.thermophilus). The genetic modifications and subsequent structural analysis of carotenoids helped clarify the carotenoid biosynthetic pathway in R. marinus. The nucleotide sequences encoding the enzymes phytoene synthase (CrtB) and the previously unidentified 1′,2′-hydratase (CruF) were found fused together and encoded by a single gene in R. marinus. Deleting only the cruF part of the gene did not result in an active CrtB enzyme. However, by deleting the entire gene and inserting the crtB gene from Thermus thermophilus, a mutant strain was obtained, producing lycopene as the sole carotenoid. The lycopene produced by TK-3 was quantified as 0.49 g/kg CDW (cell dry weight).
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| 12. |
- Meagher, N. S., et al.
(författare)
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A combination of the immunohistochemical markers CK7 and SATB2 is highly sensitive and specific for distinguishing primary ovarian mucinous tumors from colorectal and appendiceal metastases
- 2019
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Ingår i: Modern Pathology. - : Elsevier BV. - 0893-3952. ; 32, s. 1834-1846
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Tidskriftsartikel (refereegranskat)abstract
- Primary ovarian mucinous tumors can be difficult to distinguish from metastatic gastrointestinal neoplasms by histology alone. The expected immunoprofile of a suspected metastatic lower gastrointestinal tumor is CK7−/CK20+/CDX2+/PAX8−. This study assesses the addition of a novel marker SATB2, to improve the diagnostic algorithm. A test cohort included 155 ovarian mucinous tumors (105 carcinomas and 50 borderline tumors) and 230 primary lower gastrointestinal neoplasms (123 colorectal adenocarcinomas and 107 appendiceal neoplasms). All cases were assessed for SATB2, PAX8 CK7, CK20, and CDX2 expression on tissue microarrays. Expression was scored in a 3-tier system as absent, focal (1–50% of tumor cells) and diffuse (>50% of tumor cells) and then categorized into either absent/present or nondiffuse/diffuse. SATB2 and PAX8 expression was further evaluated in ovarian tumors from an international cohort of 2876 patients (expansion cohort, including 159 mucinous carcinomas and 46 borderline mucinous tumors). The highest accuracy of an individual marker indistinguishing lower gastrointestinal from ovarian mucinous tumors was CK7 (91.7%, nondiffuse/diffuse cut-off) followed by SATB2 (88.8%, present/absent cut-off). The most effective combination was CK7 and SATB2 with accuracy of 95.3% using the 3-tier interpretation, absent/focal/diffuse. This combination outperformed the standard clinical set of CK7, CK20 and CDX2 (87.5%). Re-evaluation of outlier cases confirmed ovarian origin for all but one case. The accuracy of SATB2 was confirmed in the expansion cohort (91.5%). SATB2 expression was also detected in 15% of ovarian endometrioid carcinoma but less than 5% of other ovarian histotypes. A simple two marker combination of CK7 and SATB2 can distinguish lower gastrointestinal from ovarian primary mucinous tumors with greater than 95% accuracy. PAX8 and CDX2 have value as second-line markers. The utility of CK20 in this setting is low and this warrants replacement of this marker with SATB2 in clinical practice. © 2019, The Author(s), under exclusive licensc to United States & Canadian Academy of Pathology.
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| 13. |
- Sigurdsson, Snaevar, et al.
(författare)
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Comprehensive evaluation of the genetic variants of interferon regulatory factor 5 (IRF5) reveals a novel 5 bp length polymorphism as strong risk factor for systemic lupus erythematosus
- 2008
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 17:6, s. 872-881
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Tidskriftsartikel (refereegranskat)abstract
- We analyzed a comprehensive set of single-nucleotide polymorphisms (SNPs) and length polymorphisms in the interferon regulatory factor 5 (IRF5) gene for their association with the autoimmune disease systemic lupus erythematosus (SLE) in 485 Swedish patients and 563 controls. We found 16 SNPs and two length polymorphisms that display association with SLE (P < 0.0005, OR > 1.4). Using a Bayesian model selection and averaging approach we identified parsimonious models with exactly two variants of IRF5 that are independently associated with SLE. The variants of IRF5 with the highest posterior probabilities (1.00 and 0.71, respectively) of being causal in SLE are a SNP (rs10488631) located 3' of IRF5, and a novel CGGGG insertion-deletion (indel) polymorphism located 64 bp upstream of the first untranslated exon (exon 1A) of IRF5. The CGGGG indel explains the association signal from multiple SNPs in the IRF5 gene, including rs2004640, rs10954213 and rs729302 previously considered to be causal variants in SLE. The CGGGG indel contains three or four repeats of the sequence CGGGG with the longer allele containing an additional SP1 binding site as the risk allele for SLE. Using electrophoretic mobility shift assays we show increased binding of protein to the risk allele of the CGGGG indel and using a minigene reporter assay we show increased expression of IRF5 mRNA from a promoter containing this allele. Increased expression of IRF5 protein was observed in peripheral blood mononuclear cells from SLE patients carrying the risk allele of the CGGGG indel. We have found that the same IRF5 allele also confers risk for inflammatory bowel diseases and multiple sclerosis, suggesting a general role for IRF5 in autoimmune diseases.
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| 14. |
- Sigurdsson, S, et al.
(författare)
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Polymorphisms in the tyrosine kinase 2 and interferon regulatory factor 5 genes are associated with systemic lupus erythematosus
- 2005
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 76:3, s. 528-37
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Tidskriftsartikel (refereegranskat)abstract
- Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease caused by both genetic and environmental factors. Genome scans in families with SLE point to multiple potential chromosomal regions that harbor SLE susceptibility genes, and association studies in different populations have suggested several susceptibility alleles for SLE. Increased production of type I interferon (IFN) and expression of IFN-inducible genes is commonly observed in SLE and may be pivotal in the molecular pathogenesis of the disease. We analyzed 44 single-nucleotide polymorphisms ( SNPs) in 13 genes from the type I IFN pathway in 679 Swedish, Finnish, and Icelandic patients with SLE, in 798 unaffected family members, and in 438 unrelated control individuals for joint linkage and association with SLE. In two of the genes - the tyrosine kinase 2 (TYK2) and IFN regulatory factor 5 (IRF5) genes - we identified SNPs that displayed strong signals in joint analysis of linkage and association (unadjusted P < 10(-7)) with SLE. TYK2 binds to the type I IFN receptor complex and IRF5 is a regulator of type I IFN gene expression. Thus, our results support a disease mechanism in SLE that involves key components of the type I IFN system.
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| 15. |
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| 16. |
- Allahgholi, Leila, et al.
(författare)
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Composition analysis and minimal treatments to solubilize polysaccharides from the brown seaweed Laminaria digitata for microbial growth of thermophiles
- 2020
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Ingår i: Journal of Applied Phycology. - : Springer Science and Business Media LLC. - 0921-8971 .- 1573-5176. ; 32:3, s. 1933-1947
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Tidskriftsartikel (refereegranskat)abstract
- Brown macroalgae (Phaeophyta) hold high potential as feedstock for biorefineries due to high biomass productivity and carbohydrate content. They are, however, a challenging, unconventional feedstock for microbial refining and several processing problems need to be solved to make them a viable option. Pre-treatment is necessary to enhance accessibility and solubility of the biomass components but should be minimal and mild to assure sustainable and cost-effective processing. Here, two routes to pre-treatLaminaria digitata to release polysaccharides were investigated: hot water pre-treatment by autoclaving (121 °C, 20 min or 60 min) and a two-step extraction with mild acid (0.1 M HCl) followed by alkaline treatment. Hot water pre-treatment resulted in partial extraction of a mixture of polysaccharides consisting of alginate, fucoidan and laminarin. After mild acid pre-treatment, alginate was found in the remaining insoluble residues and was extracted in a second step via alkaline treatment using Na2CO3 (0.15 M) at 80 °C and CaCl2 (10%) for the precipitation. In addition to carbohydrates, a fraction of other components such as proteins, phenolic compounds, minerals and trace elements was detected in the extracts. Cultivation of the thermophilic bacterial strains Rhodothermus marinus DSM 16675 and Bacillus methanolicus MGA3 (ATCC 53907) in media supplemented with the respective extracts resulted in growth of both strains, indicating that they were able to utilize the available carbon source for growth. R. marinus displayed the highest cell density in the medium containing the extract from acid pre-treatment, whereas B. methanolicus growth was highest with the extract from hot water pre-treatment.
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| 17. |
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| 18. |
- Delgado-Vega, Angélica M., et al.
(författare)
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Whole Exome Sequencing of Patients from Multicase Families with Systemic Lupus Erythematosus Identifies Multiple Rare Variants
- 2018
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 8775-
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Tidskriftsartikel (refereegranskat)abstract
- In an effort to identify rare alleles associated with SLE, we have performed whole exome sequencing of the most distantly related affected individuals from two large Icelandic multicase SLE families followed by Ta targeted genotyping of additional relatives. We identified multiple rare likely pathogenic variants in nineteen genes co-segregating with the disease through multiple generations. Gene co-expression and protein-protein interaction analysis identified a network of highly connected genes comprising several loci previously implicated in autoimmune diseases. These genes were significantly enriched for immune system development, lymphocyte activation, DNA repair, and V(D)J gene recombination GO-categories. Furthermore, we found evidence of aggregate association and enrichment of rare variants at the FAM71E1/EMC10 locus in an independent set of 4,254 European SLE-cases and 4,349 controls. Our study presents evidence supporting that multiple rare likely pathogenic variants, in newly identified genes involved in known disease pathogenic pathways, segregate with SLE at the familial and population level.
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| 19. |
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| 20. |
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| 21. |
- Grondal, G, et al.
(författare)
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Increased T-lymphocyte apoptosis/necrosis and IL-10 producing cells in patients and their spouses in Icelandic systemic lupus erythematosus multicase families
- 2002
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Ingår i: Lupus. - : SAGE Publications. - 0961-2033 .- 1477-0962. ; 11:7, s. 435-442
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to evaluate apoptosis and production of IL-10 in SLE patients, their spouses and first-degree relatives in Icelandic SLE multicase families. Previously, increased IL-10 production has been found in all three groups. As IL-10 has been found to induce apoptosis in SLE, the percentage of lymphocytes undergoing apoptosis was evaluated, as well as the possible correlation between apoptosis and IL-10 production. Apoptosis and IL-10 production were studied in SLE patients (n = 12) from SLE multicase families and their spouses (n = 12) and a matched control group of healthy individuals(n = 10). The proportion of T and B lymphocytes undergoing apoptosis at 0, 24, 48 and 72 h was detected by flow cytometry using Annexin V and PI staining and the rate of apoptosis was calculated. IL-10 production was studied simultaneously by ELISpot analysis of freshly isolated peripheral blood mononuclear cells. In addition, T lymphocyte apoptosis at t = 0 was investigated in a group of non-household first-degree relatives (n = 10) and controls (n = 10). Antinuclear and antilymphocyte antibodies were analysed in all the groups. The SLE patients as a group had a significantly increased percentage of T lymphocytes in apoptosis at 0 and 48 h and a significantly higher number of IL-10 producing cells as compared with the healthy controls (P = 0.03, 0.02 and 0.03, respectively). The spouses also had significantly increased percentage of T lymphocytes in apoptosis (t = 0) and a significantly higher number of IL-10-producing cells when compared with healthy controls (P = 0.01 and 0.02, respectively). There were no significant differences between the patients and their spouses. For apoptosis of B lymphocytes no difference was found between the groups. The SLE patients as a group had the highest rate of apoptosis. No correlation between the degree and rate of apoptosis and the number of IL-10-producing cells was detected. The first-degree relatives did not have increased percentage of T lymphocytes undergoing apoptosis at t = 0 compared with healthy controls. The SLE patients had higher titres of ANA compared with the other groups. No correlation was detected between the ANA titre and the percentage of lymphocytes undergoing apoptosis. There was no correlation between disease activity as measured by SLEDAI and apoptosis. In conclusion, our results suggest that environmental factors common to both SLE patients and their spouses are associated both with the increased apoptosis and increased spontaneousproduction of IL-10, thus providing support for the notion that both environmental and genetic factors influencing apoptosis are of importance for the development of SLE.
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| 22. |
- Johanneson, B, et al.
(författare)
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A comparison of genome-scans performed in multicase families with systemic lupus erythematosus from different population groups
- 1999
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Ingår i: Journal of Autoimmunity. - : Elsevier BV. - 0896-8411. ; 13, s. 137-
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Tidskriftsartikel (refereegranskat)abstract
- Systemic lupus erythematosus is a disease of unknown etiology. Multiple genetic factors are believed to be involved in its pathogenesis. In addition, and due to genetic heterogeneity, these factors and/or their combinations may be different in different ethnic groups, while some might be shared between populations. We have performed genome scans in multicase families from three different population groups, two from Northern Europe, with a high degree of homogeneity, and the third from a recently admixed population of Mexican Mestizos. Although our family material is relatively small, the results presented here show that using family sets from well defined populations are sufficient to detect susceptibility loci for SLE. Our results also reveal the chromosomal regions most likely to contain susceptibility genes for SLE.
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| 23. |
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| 24. |
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| 25. |
- Johansson, P., et al.
(författare)
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Highly increased risk of fracture in patients with myeloproliferative neoplasm
- 2021
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Ingår i: Leukemia & Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 62:1, s. 211-217
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Tidskriftsartikel (refereegranskat)abstract
- The risk for hip and vertebral fracture was determined in 10,752 patients diagnosed with myeloproliferative neoplasms (MPN) in Sweden 1995-2015. The mean follow-up time were 6.34 years. Five percent developed hip fracture and 1.3% a vertebral fracture. There was a significant increased risk for fracture among the MPN patients compared with the Swedish population. The ratio of observed (obs) and expected (exp) number of hip fracture in all MPN patients, polycythemia vera (PV), essential thrombocythemia and MPN undetermined (MPNu) was 1.20 (95% confidence interval (CI): 1.10-1.31), 1.37 (95% CI: 1.19-1.58), 1.02 (95% CI: 0.87-1.19), and 1.28 (95% CI: 1.07-1.52), respectively. Corresponding figures for vertebral fractures were 1.94 (95% CI: 1.64-2.29), 2.09 (95% CI: 1.56-2.75), 1.50 (95% CI: 1.06-2.07) and 2.47 (95% CI: 1.77-3.35), respectively. Patients with MPN had an increased risk of hip and vertebral fracture, especially patients with PV and MPNu in comparison with the entire Swedish population.
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| 26. |
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| 27. |
- Kristjansdottir, Hallgerdur Lind, et al.
(författare)
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Anemia is associated with increased risk of non-vertebral osteoporotic fractures in elderly men: the MrOS Sweden cohort
- 2022
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Ingår i: Archives of Osteoporosis. - : Springer Science and Business Media LLC. - 1862-3522 .- 1862-3514. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- This study includes 1005 men from the Gothenburg part of the Osteoporotic Fracture in Men Study (MrOS). Included are 66 men with anemia (hemoglobin < 130 g/L). The follow-up time was up to 16 years, and the main results are that anemia is associated with all fractures and non-vertebral osteoporotic fractures. Introduction Anemia and osteoporotic fractures are conditions that are associated with increased morbidity and mortality. Clinical studies have suggested that anemia can be used as a predictor of future osteoporotic fractures. Method Men from the Osteoporotic Fractures in Men Study (MrOS) Sweden, Gothenburg, with available hemoglobin (Hb) values (n = 1005, median age 75.3 years (SD 3.2)), were included in the current analyses. Of these, 66 suffered from anemia, defined as Hb < 130 g/L. Median follow-up time for fracture was 10.1 years and the longest follow-up time was 16.1 years. Results Men with anemia had, at baseline, experienced more falls and had a higher prevalence of diabetes, cancer, prostate cancer, hypertension, and stroke. Anemia was not statistically significantly associated with bone mineral density (BMD). Men with anemia had higher serum levels of fibroblast growth factor 23 (iFGF23) (p < 0.001) and phosphate (p = 0.001) and lower serum levels of testosterone (p < 0.001) and estradiol (p < 0.001). Moreover, men with anemia had an increased risk of any fracture (hazard ratio (HR) 1.97, 95% CI 1.28-3.02) and non-vertebral osteoporotic fracture (HR 2.15, 95% CI 1.18-3.93), after adjustment for age and total hip BMD, in 10 years. The risk for any fracture was increased in 10 and 16 years independently of falls, comorbidities, inflammation, and sex hormones. The age-adjusted risk of hip fracture was increased in men with anemia (HR 2.32, 95% CI 1.06-5.12), in 10 years, although this was no longer statistically significant after further adjustment for total hip BMD. Conclusions Anemia is associated with an increased risk for any fracture and non-vertebral osteoporotic fracture in elderly men with a long follow-up time. The cause is probably multifactorial and our results support that anemia can be used as a predictor for future fracture.
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| 28. |
- Kristjansdottir, Hallgerdur Lind, et al.
(författare)
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High Plasma Erythropoietin Predicts Incident Fractures in Elderly Men with Normal Renal Function : The MrOS Sweden Cohort
- 2020
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Ingår i: Journal of Bone and Mineral Research. - : WILEY. - 0884-0431 .- 1523-4681. ; 35:2, s. 298-305
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Tidskriftsartikel (refereegranskat)abstract
- Preclinical studies on the role of erythropoietin (EPO) in bone metabolism are contradictory. Regeneration models indicate an anabolic effect on bone healing, whereas models on physiologic bone remodeling indicate a catabolic effect on bone mass. No human studies on EPO and fracture risk are available. It is known that fibroblast growth factor 23 (FGF23) affects bone mineralization and that serum concentration of FGF23 is higher in men with decreased estimated glomerular filtration rate (eGFR). Recently, a direct association between EPO and FGF23 has been shown. We have explored the potential association between EPO and bone mineral density (BMD), fracture risk, and FGF23 in humans. Plasma levels of EPO were analyzed in 999 men (aged 69 to 81 years), participating in the Gothenburg part of the population-based Osteoporotic Fractures in Men (MrOS) study, MrOS Sweden. The mean +/- SD EPO was 11.5 +/- 9.0 IU/L. Results were stratified by eGFR 60 mL/min. For men with eGFR >= 60 mL/min (n = 728), EPO was associated with age (r = 0.13, p < 0.001), total hip BMD (r = 0.14, p < 0.001), intact (i)FGF23 (r = 0.11, p = 0.004), and osteocalcin (r = -0.09, p = 0.022). The association between total hip BMD and EPO was independent of age, body mass index (BMI), iFGF23, and hemoglobin (beta = 0.019, p < 0.001). During the 10-year follow-up, 164 men had an X-ray-verified fracture, including 117 major osteoporotic fractures (MOF), 39 hip fractures, and 64 vertebral fractures. High EPO was associated with higher risk for incident fractures (hazard ratio [HR] = 1.43 per tertile EPO, 95% confidence interval [CI] 1.35-1.63), MOF (HR = 1.40 per tertile EPO, 95% CI 1.08-1.82), and vertebral fractures (HR = 1.42 per tertile EPO, 95% CI 1.00-2.01) in a fully adjusted Cox regression model. In men with eGFR<60 mL/min, no association was found between EPO and BMD or fracture risk. We here demonstrate that high levels of EPO are associated with increased fracture risk and increased BMD in elderly men with normal renal function.
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| 29. |
- Kristjansdottir, Hallgerdur Lind, et al.
(författare)
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High platelet count is associated with low bone mineral density: The MrOS Sweden cohort.
- 2021
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Ingår i: Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 32:5, s. 865-871
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Tidskriftsartikel (refereegranskat)abstract
- In elderly ambulatory men, high platelet and high neutrophil counts are related to low bone mineral density (BMD), after adjustment for relevant covariates. Low hemoglobin (hgb) is even associated with low BMD, but this relationship seems to be dependent on estradiol and osteocalcin.Blood and bone cells exist in close proximity to each other in the bone marrow. Accumulating evidence, from both preclinical and clinical studies, indicates that these cell types are interconnected. Our hypothesis was that BMD measurements are associated with blood count variables and bone remodeling markers.We analyzed blood count variables, bone remodeling markers, and BMD, in subjects from the MrOS cohort from Gothenburg, Sweden. Men with at least one blood count variable (hgb, white blood cell count, or platelet count) analyzed were included in the current analysis (n=1005), median age 75.3years (range 69-81years).Our results show that high platelet counts were related to low BMD at all sites (total hip BMD; r=-0.11, P=0.003). No statistically significant association was seen between platelet counts and bone remodeling markers. Neutrophil counts were negatively associated with total body BMD (r=-0.09, P=0.006) and total hip BMD (r=-0.08, P=0.010), and positively related to serum ALP (r=0.15, P<0.001). Hgb was positively related to total hip BMD (r=0.16, P<0.001), and negatively to serum osteocalcin (r=-0.13, P<0.001). The association between platelet and neutrophil counts and total hip BMD was statistically significant after adjustments for other covariates, but the association between hgb and total hip BMD was dependent on estradiol and osteocalcin.Our observations support the hypothesis of an interplay between blood and bone components.
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| 30. |
- Kristjansdottir, Hallgerdur Lind, et al.
(författare)
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High Serum Serotonin Predicts Increased Risk for Hip Fracture and Nonvertebral Osteoporotic Fractures : The MrOS Sweden Study
- 2018
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431. ; 33:9, s. 1560-1567
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Tidskriftsartikel (refereegranskat)abstract
- Because several studies have implicated serotonin as a regulator of bone mass, we here explore its potential association on fracture risk and falls, as on bone mineral density (BMD) and muscle strength, in humans. Serum levels of serotonin were analyzed in 950 men (aged 69 to 81 years), participating in the Gothenburg part of the population-based study MrOS Sweden. Men taking selective serotonin reuptake inhibitors (SSRIs) had a mean value of 31.2 μg/L compared with 159.4 μg/L in those not taking SSRIs. SSRI users were excluded from further analysis. During 10-year follow-up, 224 men exhibited fractures, including 97 nonvertebral osteoporotic fractures (57 hip fractures), and 86 vertebral fractures. Serotonin was associated with hip fracture in linear analysis (hazard ratio [HR] = 1.27, 95% confidence interval [CI] 1.03–1.58) and to all fractures in a nonlinear manner, when quintiles of serotonin was included in quadratic terms (HR = 1.12, 95% CI 1.04–1.21). Men in serotonin quintile 5 had, in multivariable analysis, a HR of 2.30 (95% CI 1.31–4.02) for hip fracture and 1.82 (95% CI 1.17–2.85) for nonvertebral fractures compared with men in quintiles 1 to 4. Men in quintile 1 had, in multivariable analysis, a HR of 1.76 (95% CI 1.03–2.99) for nonvertebral fractures compared with men in quintiles 2 to 4. No association was found with vertebral fractures. Individuals in serotonin quintile 1 had higher prevalence of falls compared with quintiles 2 to 5 (odds ratio = 1.90, 95% CI 1.26–2.87). Serotonin was positively associated with hand-grip strength (r = 0.08, p = 0.02) and inversely with hip BMD (r = −0.10, p = 0.003). To assess the association between SSRIs and falls and fractures, the total MrOS Sweden cohort was examined (n = 3014). SSRI users (n = 90) had increased prevalence of falls (16% versus 33%, p = 0.0001) and increased rate of incident fractures (28.0 versus 44.7 per 1000 person-years, p = 0.018). We present novel data showing that high levels of serotonin predict an increased risk for hip fracture and nonvertebral osteoporotic fractures.
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| 31. |
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| 32. |
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| 33. |
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| 34. |
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| 35. |
- Saevarsdottir, S., et al.
(författare)
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Mannan-binding lectin and complement C4A in Icelandic multicase families with systemic lupus erythematosus
- 2006
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 65:11, s. 1462-7
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To determine whether low mannan-binding lectin (MBL) and C4A null alleles (C4AQ0) are associated with systemic lupus erythematosus (SLE) in multicase families with SLE. Methods: Low MBL level was determined by measuring serum levels and by genotyping for mutant structural (B/C/D, designated as 0) and promoter (LX) alleles (by real-time polymerase chain reaction). C4AQ0 was detected by protein electrophoresis and corroborated with haplotype and genotype analysis. In nine Icelandic families, 24 patients with SLE were compared with 83 first-degree and 23 second-degree relatives without SLE. Twenty four unrelated family members and a population group of 330 Icelanders served as controls. Results: Overall, the frequency of low MBL genotypes (0/0, LX/0 and wild-type/0) tended to be higher in patients with SLE than in their first-degree and second-degree relatives (p = 0.06), but the frequency was similar in the families and in the controls (p = 0.6). The frequency of C4AQ0 was, however, increased in patients and their relatives compared with that in the controls (p = 0.04). The combination of low MBL genotypes and C4AQ0 was found more often in the patients than in their relatives (p = 0.03) and controls (p = 0.02). However, low MBL level was observed only in patients and first-degree relatives in five of the nine multicase families. In these five families, patients with SLE had low MBL genotypes more often (64%) than their first-degree (38%) and second-degree (0%) relatives (p = 0.001), and the patients with SLE also had, accordingly, lower MBL levels than their relatives (p = 0.001). Conclusions: These findings indicate that low MBL levels can predispose people to SLE and highlight the genetic heterogeneity of this disease.
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| 36. |
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| 37. |
- Simonsen, Ingeborg, et al.
(författare)
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Early-phase energy supply planning
- 2014
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Ingår i: Utopia revisited. - Bergen, Norway : Fagbokforlaget. - 9788245017250 ; , s. 305-327
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Bokkapitel (refereegranskat)
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| 38. |
- Wrande, T., et al.
(författare)
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Live birth, cumulative live birth and perinatal outcome following assisted reproductive treatments using donor sperm in single women vs. women in lesbian couples: a prospective controlled cohort study
- 2022
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Ingår i: Journal of Assisted Reproduction and Genetics. - : Springer Science and Business Media LLC. - 1058-0468 .- 1573-7330. ; 39, s. 629-637
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Assisted reproductive technology (ART) treatments with donor sperm have been allowed for women in lesbian relationships (WLR) since 2005 in Sweden, but for single women (SW), these became approved only recently in 2016. This study was conducted to compare the outcomes of ART treatments in SW vs. WLR. Methods This is a prospective controlled cohort study of 251 women undergoing intrauterine insemination (D-IUI) or in vitro fertilization (D-IVF) using donor sperm between 2017 and 2019 at the department of Reproductive Medicine, Karolinska University Hospital. The cohort comprised 139 SW and 112 WLR. The main outcomes included differences in live birth rate (LBR) and cumulative live birth rate (cLBR) between the groups. The SW underwent 66 D-IUI and 193 D-IVF treatments and WLR underwent 255 D-IUI and 69 D-IVF treatments. Data on clinical characteristics, treatment protocols and clinical outcomes were extracted from the clinic's electronic database. The outcomes of D-IUI and D-IVF were separately assessed. Results The cohort of SW was significantly older than WLR (37.6 vs. 32.4 years, P < 0.001), and more commonly underwent IVF at first treatment (83% vs. 29%, P < 0.000). Conversely, WLR underwent more frequently D-IUI as a first treatment (71% vs. 17% of SW, P < 0.001) and more often in the natural cycle (89.9% vs. 70.8%, P = 0.019), respectively. There was no statistically significant difference in the main outcome LBR between the two groups, or between the two different types of treatment, when adjusted for age. Perinatal outcomes and cLBR were also similar among the groups. Conclusions SW were, on average, older than WLR undergoing treatment with donor sperm. No significant differences were seen in the LBR and cLBR when adjusted for age between the two groups and between the two types of treatment (D-IVF vs. D-IUI).
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