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A common missense v...
A common missense variant of LILRB5 is associated with statin intolerance and myalgia
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- Siddiqui, Moneeza K. (author)
- University of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine
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- Maroteau, Cyrielle (author)
- University of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine
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- Veluchamy, Abirami (author)
- University of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine
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- Tornio, Aleksi (author)
- University of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine
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- Tavendale, Roger (author)
- University of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine
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- Carr, Fiona (author)
- University of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine
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- Abelega, Ngu-Uma (author)
- University of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine
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- Carr, Dan (author)
- University of Liverpool, Institute of Translation Medicine
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- Bloch, Katyrzyna (author)
- University of Liverpool, Institute of Translation Medicine
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- Hallberg, Pär, 1974- (author)
- Uppsala universitet,Klinisk farmakogenomik och osteoporos
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- Yue, Qun-Ying (author)
- Medical Products Agency, Uppsala
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- Pearson, Ewan R. (author)
- University of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine
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- Colhoun, Helen M. (author)
- 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
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- Morris, Andrew D. (author)
- 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
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- Dow, Eleanor (author)
- Ninewells Hospital and Medical School
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- George, Jacob (author)
- Ninewells Hospital and Medical School
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- Pirmohamed, Munir (author)
- University of Liverpool, Institute of Translation Medicine
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- Ridker, Paul M. (author)
- Harvard Medical School, Brigham and Women’s Hospital, Department of Medicine, Preventive Medicine
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- Doney, Alex S. F. (author)
- Ninewells Hospital and Medical School
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- Alfirevic, Ana (author)
- University of Liverpool, Institute of Translation Medicine
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- Wadelius, Mia (author)
- Uppsala universitet,Klinisk farmakogenomik och osteoporos
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- Maitland-van der Zee, Anke-Hilse (author)
- Utrecht University, Utrecht Institute of Pharmaceutical Sciences, Division of Pharmacoepidemiology and Clinical Pharmacology; University of Amsterdam, Academic Medical Center, Department of Respiratory Medicine
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- Chasman, Daniel I. (author)
- Harvard Medical School, Brigham and Women’s Hospital, Department of Medicine, Preventive Medicine
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- Palmer, Colin N. A. (author)
- University of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine
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(creator_code:org_t)
- 2017-08-29
- 2017
- English.
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In: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 38:48, s. 3569-U31
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https://doi.org/10.1...
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
Keyword
- Statins
- Pharmacogenetics
- Immunogenetics
- Precision medicine
- Adverse drug reactions
- Myalgia
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Siddiqui, Moneez ...
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Maroteau, Cyriel ...
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Veluchamy, Abira ...
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Tornio, Aleksi
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Tavendale, Roger
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Carr, Fiona
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show more...
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Abelega, Ngu-Uma
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Carr, Dan
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Bloch, Katyrzyna
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Hallberg, Pär, 1 ...
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Yue, Qun-Ying
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Pearson, Ewan R.
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Colhoun, Helen M ...
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Morris, Andrew D ...
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Dow, Eleanor
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George, Jacob
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Pirmohamed, Muni ...
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Ridker, Paul M.
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Doney, Alex S. F ...
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Alfirevic, Ana
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Wadelius, Mia
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Maitland-van der ...
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Chasman, Daniel ...
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Palmer, Colin N. ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cardiac and Card ...
- Articles in the publication
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European Heart J ...
- By the university
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Uppsala University