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  • 51.
    Siddiqui, Moneeza K.
    et al.
    University of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine.
    Maroteau, Cyrielle
    University of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine.
    Veluchamy, Abirami
    University of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine.
    Tornio, Aleksi
    University of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine.
    Tavendale, Roger
    University of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine.
    Carr, Fiona
    University of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine.
    Abelega, Ngu-Uma
    University of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine.
    Carr, Dan
    University of Liverpool, Institute of Translation Medicine.
    Bloch, Katyrzyna
    University of Liverpool, Institute of Translation Medicine.
    Hallberg, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Yue, Qun-Ying
    Medical Products Agency, Uppsala.
    Pearson, Ewan R.
    University of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine.
    Colhoun, Helen M.
    University of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine; University of Edinburgh, Institute of Genetics & Molecular.
    Morris, Andrew D.
    University of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine; University of Edinburgh, Usher Institute of Population Health Sciences and Informatics.
    Dow, Eleanor
    Ninewells Hospital and Medical School.
    George, Jacob
    Ninewells Hospital and Medical School.
    Pirmohamed, Munir
    University of Liverpool, Institute of Translation Medicine.
    Ridker, Paul M.
    Harvard Medical School, Brigham and Women’s Hospital, Department of Medicine, Preventive Medicine.
    Doney, Alex S. F.
    Ninewells Hospital and Medical School.
    Alfirevic, Ana
    University of Liverpool, Institute of Translation Medicine.
    Wadelius, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Maitland-van der Zee, Anke-Hilse
    Utrecht University, Utrecht Institute of Pharmaceutical Sciences, Division of Pharmacoepidemiology and Clinical Pharmacology; University of Amsterdam, Academic Medical Center, Department of Respiratory Medicine.
    Chasman, Daniel I.
    Harvard Medical School, Brigham and Women’s Hospital, Department of Medicine, Preventive Medicine.
    Palmer, Colin N. A.
    University of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine.
    A common missense variant of LILRB5 is associated with statin intolerance and myalgia2017In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 38, no 48, p. 3569-U31Article in journal (Refereed)
    Abstract [en]

    Aims: A genetic variant in LILRB5 (leukocyte immunoglobulin-like receptor subfamily-B) (rs12975366: T > C: Asp247Gly) has been reported to be associated with lower creatine phosphokinase (CK) and lactate dehydrogenase (LDH) levels. Both biomarkers are released from injured muscle tissue, making this variant a potential candidate for susceptibility to muscle-related symptoms. We examined the association of this variant with statin intolerance ascertained from electronic medical records in the GoDARTS study.

    Methods and results: In the GoDARTS cohort, the LILRB5 Asp247 variant was associated with statin intolerance (SI) phenotypes; one defined as having raised CK and being non-adherent to therapy [odds ratio (OR) 1.81; 95% confidence interval (CI): 1.34–2.45] and the other as being intolerant to the lowest approved dose of a statin before being switched to two or more other statins (OR 1.36; 95% CI: 1.07–1.73). Those homozygous for Asp247 had increased odds of developing both definitions of intolerance. Importantly the second definition did not rely on CK elevations. These results were replicated in adjudicated cases of statin-induced myopathy in the PREDICTION-ADR consortium (OR1.48; 95% CI: 1.05–2.10) and for the development of myalgia in the JUPITER randomized clinical trial of rosuvastatin (OR1.35, 95% CI: 1.10–1.68). A meta-analysis across the studies showed a consistent association between Asp247Gly and outcomes associated with SI (OR1.34; 95% CI: 1.16–1.54).

    Conclusion: This study presents a novel immunogenetic factor associated with statin intolerance, an important risk factor for cardiovascular outcomes. The results suggest that true statin-induced myalgia and non-specific myalgia are distinct, with a potential role for the immune system in their development. We identify a genetic group that is more likely to be intolerant to their statins.

  • 52.
    Sundbaum, J. K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Lulea Univ Technol, Dept Hlth Sci, Lulea, Sweden.
    Ericsson, N.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Hallberg, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Lehto, N.
    Lulea Univ Technol, Dept Hlth Sci, Lulea, Sweden.
    Wadelius, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Baecklund, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Methotrexate treatment in rheumatoid arthritis and elevated liver enzymes: a long-term follow-up of occurrence, predictors, surveillance, and outcome in clinical practice2018In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, p. 977-977Article in journal (Other academic)
  • 53.
    Wadelius, Mia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Eriksson, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Kreutz, Reinhold
    Universitätsmedizin Berlin, Institut für Klinische Pharmakologie und Toxikologie, Berlin, Germany.
    Bondon-Guitton, Emmanuelle
    Service de Pharmacologie Médicale et Clinique, Centre Hospitalier Universitaire, Faculté de Médecine de l'Université de Toulouse, Toulouse, France.
    Ibañez, Luisa
    Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Fundació Institut Català de Farmacologia, Barcelona, Spain.
    Carvajal, Alfonso
    Centro de Estudios sobre la Seguridad de los Medicamentos, Universidad de Valladolid, Valladolid, Spain.
    Lucena, M Isabel
    S Farmacologia Clinica, Instituto de Investigación Biomedica de Málaga (IBIMA), H Universitario Virgen de la Victoria, Universidad de Málaga, CIBERehd, Madrid, Spain.
    Sancho Ponce, Esther
    Servei d'Hematologia i Banc de Sang, Hospital General de Catalunya, Sant Cugat del Vallès, Spain.
    Molokhia, Mariam
    NIHR Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London Department of Primary Care and Public Health Sciences, London, U.
    Martin, Javier
    Instituto de Parasitologia y Biomedicina Lopez-Neyra, CSIC, Granada, Spain.
    Axelsson, Tomas
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Kohnke, Hugo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Yue, Qun-Ying
    Medical Products Agency, Uppsala, Sweden.
    Magnusson, Patrik K E
    Swedish Twin Registry, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Bengtsson, Mats
    Uppsala University, Science for Life Laboratory, SciLifeLab.
    Hallberg, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sulfasalazine-Induced Agranulocytosis Is Associated With the Human Leukocyte Antigen Locus.2018In: Clinical Pharmacology and Therapeutics, ISSN 0009-9236, E-ISSN 1532-6535, Vol. 103, no 5, p. 843-853Article in journal (Refereed)
    Abstract [en]

    Agranulocytosis is a serious, although rare, adverse reaction to sulfasalazine, which is used to treat inflammatory joint and bowel disease. We performed a genome‐wide association study comprising 9,380,034 polymorphisms and 180 HLA alleles in 36 cases of sulfasalazine‐induced agranulocytosis and 5,170 population controls. Sulfasalazine‐induced agranulocytosis was significantly associated with the HLA region on chromosome 6. The top hit (rs9266634) was located close to HLA‐B, odds ratio (OR) 5.36 (95% confidence interval (CI) (2.97, 9.69) P = 2.55 × 10−8). We HLA‐sequenced a second cohort consisting of 40 cases and 142 treated controls, and confirmed significant associations with HLA‐B*08:01, OR = 2.25 (95% CI (1.02, 4.97) P = 0.0439), in particular the HLA‐B*08:01 haplotype HLA‐DQB1*02:01‐DRB1*03:01‐B*08:01‐C*07:01, OR = 3.79 (95% CI (1.63, 8.80) P = 0.0019), and with HLA‐A*31:01, OR = 4.81 (95% CI (1.52, 15.26) P = 0.0077). The number needed to test for HLA‐B*08:01 and HLA‐A*31:01 to avoid one case was estimated to be 1,500. We suggest that intensified monitoring or alternative treatment should be considered for known carriers of HLA‐B*08:01 or HLA‐A*31:01.

  • 54.
    Wadelius, Mia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Eriksson, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Smedje, H.
    Karolinska Inst, Div Child & Adolescent Psychiat, Stockholm, Sweden.
    Yue, Q. -Y
    Med Prod Agcy, Uppsala, Sweden.
    Magnusson, P. K. E.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Hallberg, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Genome‐Wide Association Study of Pandemrix‐Induced Narcolepsy in Sweden – A Possible Role for Glial Derived Neurotrophic Factor (GDNF)2018In: Basic & Clinical Pharmacology & Toxicology, ISSN 1742-7835, E-ISSN 1742-7843, Vol. 123, no S1, p. 12-13Article in journal (Other academic)
  • 55.
    Wadelius, Mia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Marshall, S. E.
    Islander, G.
    Nordang, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Karawajczyk, Malgorzata
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Yue, Q-Y
    Terreehorst, I.
    Baranova, E. V.
    Hugosson, S.
    Skoldefors, K.
    Pirmohamed, M.
    Maitland-van der Zee, A-H
    Alfirevic, A.
    Hallberg, Pär
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Palmer, C. N. A.
    Phenotype Standardization of Angioedema in the Head and Neck Region Caused by Agents Acting on the Angiotensin System2014In: Clinical Pharmacology and Therapeutics, ISSN 0009-9236, E-ISSN 1532-6535, Vol. 96, no 4, p. 477-481Article, review/survey (Refereed)
    Abstract [en]

    Angioedema is a potentially life-threatening adverse reaction to angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. To study the genetic etiology of this rare adverse event, international consortia and multicenter recruitment of patients are needed. To reduce patient heterogeneity, we have standardized the phenotype. In brief, it comprises swelling in the head and neck region that first occurs during treatment. It should not coincide with urticaria or have another likely cause such as hereditary angioedema.

  • 56.
    Watkins, Paul B.
    et al.
    Univ N Carolina, Chapel Hill, NC 27515 USA.
    Nicoletti, Paola
    Mt Sinai, Genet, Sinai, Egypt.
    Cirulli, Elizabeth
    Duke, Genet, Durham, NC USA.
    Abramson, Karen
    Duke, Genet, Durham, NC USA.
    Andrade, Raul J.
    Univ Malaga, Ugc Aparato Digest, Inst Invest Biomed Malaga IBIMA, Hosp Univ Virgen De La Victoria, Malaga, Spain;Univ Malaga, Serv Farmacol Clin, Inst Invest Biomed Malaga IBIMA, Hosp Univ Virgen De La Victoria, Malaga, Spain.
    Bjornsson, Einar
    Univ Iceland, Fac Med, Sch Hlth Sci, Reykjavik, Iceland.
    Chalasani, Naga P.
    Indiana Univ Sch Med, Div Gastroenterol & Hepatol, Indianapolis, IN 46202 USA.
    Fontana, Robert J.
    Univ Michigan, Div Gastroenterol & Hepatol, Ann Arbor, MI 48109 USA.
    Hallberg, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Li, Yi-Ju
    Duke, Genet, Durham, NC USA.
    Lucena, Maribel
    Univ Malaga, Ugc Aparato Digest, Inst Invest Biomed Malaga IBIMA, Hosp Univ Virgen De La Victoria, Malaga, Spain;Univ Malaga, Serv Farmacol Clin, Inst Invest Biomed Malaga IBIMA, Hosp Univ Virgen De La Victoria, Malaga, Spain.
    Long, Nanye
    Duke, Genet, Durham, NC USA.
    Molokhia, Miriam
    Kings Coll London, Primary Care, London, England.
    Nelson, Mathew
    Glaxosmithkline, Genet, Brentford, England.
    Odin, Joseph
    Icahn Sch Med Mt Sinai, New York, NY 10029 USA.
    Pirmohamed, Munir
    Univ Liverpool, Clin Pharmacol, Liverpool, Merseyside, England.
    Rafnar, Thorunn
    Decode, Genet, Bergen, Norway.
    Serrano, Jose
    NIH, Liver Pancreas & GI Neuroendocrine, Bldg 10, Bethesda, MD 20892 USA.
    Stefansson, Karen
    Decode, Genet, Bergen, Norway.
    Stolz, Andrew
    Univ Southern Calif, Los Angeles, CA USA.
    Daly, Ann
    Newcastle Univ, Newcastle Upon Tyne, Tyne & Wear, England.
    Aithal, Guruprasad P.
    Queens Med Ctr, Honolulu, HI USA.
    Identification of a PTPN22 Missense Variant As a General Genetic Risk Factor for Drug-Induced Liver Injury2018In: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350, Vol. 68, p. 25A-25AArticle in journal (Other academic)
12 51 - 56 of 56
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