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

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

Siddiqui, Moneeza K. (author): University of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine

Maroteau, Cyrielle (author): University of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine

Veluchamy, Abirami (author): University of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine

Tornio, Aleksi (author): University of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine

Tavendale, Roger (author): University of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine

Carr, Fiona (author): University of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine

Abelega, Ngu-Uma (author): University of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine

Carr, Dan (author): University of Liverpool, Institute of Translation Medicine

Bloch, Katyrzyna (author): University of Liverpool, Institute of Translation Medicine

Hallberg, Pär, 1974- (author): Uppsala universitet,Klinisk farmakogenomik och osteoporos

Yue, Qun-Ying (author): Medical Products Agency, Uppsala

Pearson, Ewan R. (author): University of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine

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

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

Dow, Eleanor (author): Ninewells Hospital and Medical School

George, Jacob (author): Ninewells Hospital and Medical School

Pirmohamed, Munir (author): University of Liverpool, Institute of Translation Medicine

Ridker, Paul M. (author): Harvard Medical School, Brigham and Women’s Hospital, Department of Medicine, Preventive Medicine

Doney, Alex S. F. (author): Ninewells Hospital and Medical School

Alfirevic, Ana (author): University of Liverpool, Institute of Translation Medicine

Wadelius, Mia (author): Uppsala universitet,Klinisk farmakogenomik och osteoporos

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

Chasman, Daniel I. (author): Harvard Medical School, Brigham and Women’s Hospital, Department of Medicine, Preventive Medicine

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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2017-08-29
2017
English.
In: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 38:48, s. 3569-U31

Related links:: https://doi.org/10.1...; show more...; https://uu.diva-port... (primary) (Raw object); https://academic.oup...; https://urn.kb.se/re...; https://doi.org/10.1...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

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

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