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Sökning: onr:"swepub:oai:DiVA.org:uu-339765" > A common missense v...

A common missense variant of LILRB5 is associated with statin intolerance and myalgia

Siddiqui, Moneeza K. (författare)
University of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine
Maroteau, Cyrielle (författare)
University of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine
Veluchamy, Abirami (författare)
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 (författare)
University of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine
Tavendale, Roger (författare)
University of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine
Carr, Fiona (författare)
University of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine
Abelega, Ngu-Uma (författare)
University of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine
Carr, Dan (författare)
University of Liverpool, Institute of Translation Medicine
Bloch, Katyrzyna (författare)
University of Liverpool, Institute of Translation Medicine
Hallberg, Pär, 1974- (författare)
Uppsala universitet,Klinisk farmakogenomik och osteoporos
Yue, Qun-Ying (författare)
Medical Products Agency, Uppsala
Pearson, Ewan R. (författare)
University of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine
Colhoun, Helen M. (författare)
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. (författare)
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 (författare)
Ninewells Hospital and Medical School
George, Jacob (författare)
Ninewells Hospital and Medical School
Pirmohamed, Munir (författare)
University of Liverpool, Institute of Translation Medicine
Ridker, Paul M. (författare)
Harvard Medical School, Brigham and Women’s Hospital, Department of Medicine, Preventive Medicine
Doney, Alex S. F. (författare)
Ninewells Hospital and Medical School
Alfirevic, Ana (författare)
University of Liverpool, Institute of Translation Medicine
Wadelius, Mia (författare)
Uppsala universitet,Klinisk farmakogenomik och osteoporos
Maitland-van der Zee, Anke-Hilse (författare)
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. (författare)
Harvard Medical School, Brigham and Women’s Hospital, Department of Medicine, Preventive Medicine
Palmer, Colin N. A. (författare)
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
2017
Engelska.
Ingår i: European Heart Journal. - 0195-668X .- 1522-9645. ; 38:48, s. 3569-U31
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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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.

Ämnesord

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Kardiologi (hsv//swe)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

Nyckelord

Statins
Pharmacogenetics
Immunogenetics
Precision medicine
Adverse drug reactions
Myalgia

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