Publications by authors named "Par Hallberg"

While Coronavirus disease 2019 (COVID-19) vaccines have proven to be both effective and generally safe, rare but severe adverse events following immunization (AEFIs) are described. Autoantibodies to platelet factor-4 are associated with catastrophic thrombotic AEFIs, but comprehensive investigations of other autoantibodies are lacking. We aimed to detect and describe autoantibodies targeting coagulation-related proteins in a population-wide cohort (SWEDEGENE) including AEFIs attributed to COVID-19 vaccines in Sweden.

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  • Several small genetic studies on atypical femur fractures (AFF) have been conducted, but results lacked replication; this study uses whole exome sequencing to analyze genetic factors in a larger sample of 139 European AFF cases and 196 controls.
  • The analysis identified suggestive associations with genes like PLOD2, XRN2, and SORD, although not statistically significant; replication studies showed varying consistency across populations.
  • Findings suggest that genetic factors influencing AFFs differ among individuals and highlight the need for larger studies to further understand the genetic basis of AFF.*
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  • Researchers conducted whole genome sequencing on 66 cases of CNS toxicity induced by antimicrobial drugs and 833 controls to explore genetic predispositions.
  • The study primarily examined the role of seventeen efflux transporters at the blood-brain barrier and found no significant association, but identified uncommon genetic variants linked to CNS toxicity.
  • Three specific genes—LCP1, RETSAT, and SFMBT2—were associated with the toxicity, particularly variants in LCP1 that showed strong statistical significance.
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Type I interferons act as gatekeepers against viral infection, and autoantibodies that neutralize these signaling molecules have been associated with COVID-19 severity and adverse reactions to the live-attenuated yellow fever vaccine. On this background, we sought to examine whether autoantibodies against type I interferons were associated with adverse events following COVID-19 vaccination. Our nationwide analysis suggests that type I interferon autoantibodies were not associated with adverse events after mRNA or viral-vector COVID-19 vaccines.

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  • Angioedema is a serious reaction linked to ACE inhibitors, and its causes include genetic and non-genetic factors; recent studies have begun to uncover genetic risk factors but not the full underlying mechanisms.!* -
  • Researchers analyzed data from over 1,000 European patients, discovering three significant genetic risk loci associated with ACEi-induced angioedema, one of which has not been previously noted.!* -
  • The findings underscored the role of bradykinin signaling and coagulation pathways while suggesting new genetic candidates involved in angioedema, highlighting similar genetic effects in both European and African-American patients.!*
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Introduction: In addition to identifying new safety signals, pharmacovigilance databases could be used to identify potential risk factors for adverse drug reactions (ADRs).

Objective: To evaluate whether data mining in a pharmacovigilance database can be used to identify known and possible novel risk factors for ADRs, for use in pharmacovigilance practice.

Method: Exploratory data mining was performed within the Swedish national database of spontaneously reported ADRs.

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  • * The study analyzed over 6,000 NT1 cases and identified new genetic associations (e.g., CD207, NAB1) tied to immune response, particularly involving T cells.
  • * Results suggest that genetic factors in NT1 also relate to other autoimmune diseases, indicating a shared immune mechanism influenced by environmental factors like infections and vaccinations.
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  • Apixaban is an oral anticoagulant aimed at preventing strokes in atrial fibrillation patients, but some individuals may experience bleeding or ineffectiveness due to drug exposure issues.
  • Researchers conducted a genome-wide association study with 1,325 participants to identify genetic factors impacting how apixaban works in the body, and while no overall genetic variants were found to significantly alter drug exposure, a specific variant in a drug transporter gene was linked to increased levels of apixaban.
  • Although this genetic variant resulted in higher drug exposure, it was not correlated with an increased risk of bleeding or thromboembolic events, indicating a need for further research to assess its clinical significance.
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  • A genome-wide association study (GWAS) was conducted on 346 rheumatoid arthritis (RA) patients starting low-dose methotrexate (MTX) to find genetic variants linked to increased levels of alanine aminotransferase (ALT).
  • The study focused on two specific outcomes within the first six months of MTX treatment: ALT levels exceeding 1.5 times the normal upper limit and the maximum observed ALT levels.
  • Significant associations were found for the variants rs72783407 (linked to maximum ALT levels) and rs60427389 (tentatively linked to ALT levels >1.5 × ULN), including links to genes related to male fertility and inflammation.
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Angioedema is a relatively rare but potentially life-threatening adverse reaction to angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs). As with hereditary forms of angioedema (HAE), this adverse reaction is mediated by bradykinin. Research suggests that ACEi/ARB-induced angioedema has a multifactorial etiology.

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The immunosuppressant drug azathioprine is associated with a 4% risk of acute pancreatitis in patients with inflammatory bowel disease (IBD). Studies have demonstrated an increased risk in carriers of HLA-DQA1*02:01 and HLA-DRB1*07:01. We investigated whether these human leukocyte antigen (HLA) types were associated with azathioprine-induced pancreatitis also in Swedish patients with IBD, and whether the type of disease affected the association.

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  • * Conducted genome-wide association studies with 198 RA patients, focusing on maximum ALT levels and ALT levels exceeding 1.5 times the normal range within the first 6 months of MTX.
  • * Found significant associations between ALT elevation and specific genetic variants, including rs72675408, which may influence gene expression related to rheumatoid arthritis pathogenesis.
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  • Angioedema is a serious adverse reaction linked to ACE inhibitors, and understanding genetic factors may help identify at-risk patients.
  • A genomewide association study was conducted to find genetic connections to ACE inhibitor-associated angioedema using two cohorts of patients treated with ACE inhibitors.
  • The study identified a significant genetic marker on chromosome 14q32.2 (variant rs34485356) associated with increased angioedema risk, and this finding was confirmed in a separate cohort.
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  • Agranulocytosis is a serious but rare side effect linked to metamizole, an analgesic popular in countries like Switzerland and Germany, and its underlying causes are not yet understood.
  • Researchers conducted a multi-center study to find genetic factors that might make people susceptible to this adverse reaction, analyzing data from various European populations without finding strong associations.
  • However, they did discover two candidate genetic loci on chromosome 9 that show potential relevance to the condition, which could guide future studies exploring the mechanisms behind agranulocytosis related to metamizole.
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  • Agranulocytosis is a serious condition linked to taking metamizole (dipyrone) and involves a harmful decrease in a type of white blood cell, with potential genetic factors contributing to vulnerability.
  • This study aimed to find any link between genetic variants in HLA genes and the risk of developing metamizole-induced agranulocytosis (MIA) among European patients, focusing on a Swiss cohort.
  • Although eight candidate alleles were identified, only one showed a significant connection to MIA in the Swiss group, and no consistent associations were found across cohorts from Switzerland, Germany, and Spain.
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  • Angioedema in the head and neck due to ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) is rare but can be life-threatening, with limited studies on genetic variants linked to this reaction.
  • Researchers analyzed genetic data from 1,066 participants, including 408 with angioedema and 658 controls, finding a significant connection between a common variant in the F5 gene (factor V Leiden) and an increased risk of angioedema.
  • The study also identified rare variants in the F5 gene that contribute to higher risks of ACEI or ARB-induced angioedema, supported by a genome-wide association study confirming the link with the F5 Leiden variant.
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  • * Researchers analyzed data from a cohort of Swedish patients and identified potential genetic links, particularly focusing on the KCNMA1 gene, which showed a significant association with angioedema risk.
  • * Although initial findings did not replicate in a separate group, a combined analysis indicated that specific genetic variants could raise the likelihood of developing angioedema by 1.62 times, suggesting further research into genetic screening for patients taking these medications.
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To investigate whether variants of , and are associated with ALT elevation in rheumatoid arthritis patients starting methotrexate (MTX). Clinical and laboratory data were collected from the start of MTX treatment. Genotyping of , and was performed.

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SWEDEGENE is a Swedish nation-wide sample collection established to facilitate studies of clinical and genetic risk factors for adverse drug reactions (ADRs). Most cases are recruited among patients reported to the ADR registry at the Swedish Medical Products Agency by health-care professionals. Clinical data are collected both from medical and laboratory records and through interviews using standardized questionnaires.

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Atypical fracture of the femur is a well-documented adverse reaction to antiresorptive treatment with bisphosphonates. Although there has been significant gain of knowledge during the past decade, the pathogenesis of this type of fracture is still poorly understood. We present an update on the evidence in regard to epidemiology, pathophysiology, and management of atypical fractures.

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Aims: Statin-related myopathy (SRM), which includes rhabdomyolysis, is an uncommon but important adverse drug reaction because the number of people prescribed statins world-wide is large. Previous association studies of common genetic variants have had limited success in identifying a genetic basis for this adverse drug reaction. We conducted a multi-site whole-exome sequencing study to investigate whether rare coding variants confer an increased risk of SRM.

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Carbamazepine (CBZ) causes life-threating T-cell-mediated hypersensitivity reactions, including serious cutaneous adverse reactions (SCARs) and drug-induced liver injury (CBZ-DILI). In order to evaluate shared or phenotype-specific genetic predisposing factors for CBZ hypersensitivity reactions, we performed a meta-analysis of two genomewide association studies (GWAS) on a total of 43 well-phenotyped Northern and Southern European CBZ-SCAR cases and 10,701 population controls and a GWAS on 12 CBZ-DILI cases and 8,438 ethnically matched population controls. HLA-A*31:01 was identified as the strongest genetic predisposing factor for both CBZ-SCAR (odds ratio (OR) = 8.

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Aim: To assess predictors of alanine aminotransferase (ALT) elevation in methotrexate (MTX) treated rheumatoid arthritis (RA) patients, and to describe the monitoring of liver enzymes, including handling and outcome of elevated ALT.

Methods: All RA patients starting MTX in January, 2005 to April, 2013 at a rheumatology clinic, (Uppsala University Hospital, Sweden) were identified from electronic medical records. Clinical and laboratory data were obtained from medical records, supplemented by telephone interviews.

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Atypical femoral fracture is a well-documented adverse reaction to bisphosphonates. It is strongly related to duration of bisphosphonate use, and the risk declines rapidly after drug withdrawal. The mechanism behind bisphosphonate-associated atypical femoral fracture is unclear, but a genetic predisposition has been suggested.

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Background: The incidence of narcolepsy rose sharply after the swine influenza A (H1N1) vaccination campaign with Pandemrix. Narcolepsy is an immune-related disorder with excessive daytime sleepiness. The most frequent form is strongly associated with HLA-DQB1*06:02, but only a minority of carriers develop narcolepsy.

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