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A common missense v...
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Siddiqui, Moneeza K.University of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine
(författare)
A common missense variant of LILRB5 is associated with statin intolerance and myalgia
- Artikel/kapitelEngelska2017
Förlag, utgivningsår, omfång ...
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2017-08-29
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Oxford University Press (OUP),2017
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electronicrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:uu-339765
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-339765URI
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https://doi.org/10.1093/eurheartj/ehx467DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
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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.
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Biuppslag (personer, institutioner, konferenser, titlar ...)
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Maroteau, CyrielleUniversity of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine
(författare)
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Veluchamy, AbiramiUniversity of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine
(författare)
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Tornio, AleksiUniversity of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine
(författare)
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Tavendale, RogerUniversity of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine
(författare)
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Carr, FionaUniversity of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine
(författare)
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Abelega, Ngu-UmaUniversity of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine
(författare)
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Carr, DanUniversity of Liverpool, Institute of Translation Medicine
(författare)
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Bloch, KatyrzynaUniversity of Liverpool, Institute of Translation Medicine
(författare)
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Hallberg, Pär,1974-Uppsala universitet,Klinisk farmakogenomik och osteoporos(Swepub:uu)pahal677
(författare)
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Yue, Qun-YingMedical Products Agency, Uppsala
(författare)
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Pearson, Ewan R.University of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine
(författare)
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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
(författare)
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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
(författare)
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Dow, EleanorNinewells Hospital and Medical School
(författare)
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George, JacobNinewells Hospital and Medical School
(författare)
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Pirmohamed, MunirUniversity of Liverpool, Institute of Translation Medicine
(författare)
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Ridker, Paul M.Harvard Medical School, Brigham and Women’s Hospital, Department of Medicine, Preventive Medicine
(författare)
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Doney, Alex S. F.Ninewells Hospital and Medical School
(författare)
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Alfirevic, AnaUniversity of Liverpool, Institute of Translation Medicine
(författare)
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Wadelius, MiaUppsala universitet,Klinisk farmakogenomik och osteoporos(Swepub:uu)miawadel
(författare)
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Maitland-van der Zee, Anke-HilseUtrecht University, Utrecht Institute of Pharmaceutical Sciences, Division of Pharmacoepidemiology and Clinical Pharmacology; University of Amsterdam, Academic Medical Center, Department of Respiratory Medicine
(författare)
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Chasman, Daniel I.Harvard Medical School, Brigham and Women’s Hospital, Department of Medicine, Preventive Medicine
(författare)
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Palmer, Colin N. A.University of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine
(författare)
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University of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical MedicineUniversity of Liverpool, Institute of Translation Medicine
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:European Heart Journal: Oxford University Press (OUP)38:48, s. 3569-U310195-668X1522-9645
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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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visa fler...
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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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