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Drug Metabolism and Personalized Therapy

Official journal of the European Society of Pharmacogenomics and Personalised Therapy

Editor-in-Chief: Llerena, Adrián

Editorial Board: Benjeddou, Mongi / Chen, Bing / Dahl, Marja-Liisa / Devinsky, Ferdinand / Hirata, Rosario / Hubacek, Jaroslav A. / Ingelman-Sundberg, Magnus / Maitland-van der Zee, Anke-Hilse / Manolopoulos, Vangelis G. / Marc, Janja / Melichar, Bohuslav / Meyer, Urs A. / Nair, Sujit / Nofziger, Charity / Peiro, Ana / Sadee, Wolfgang / Salazar, Luis A. / Simmaco, Maurizio / Turpeinen, Miia / Schaik, Ron / Shin, Jae-Gook / Visvikis-Siest, Sophie / Zanger, Ulrich M.

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Volume 33, Issue 1

Issues

Effect of SLCO1B1 gene polymorphisms and vitamin D on statin-induced myopathy

Baraa Alghalyini
  • Department of Family Medicine, College of Medicine Alfaisal University, Riyadh, Kingdom of Saudi Arabia
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/ Said El Shamieh
  • Corresponding author
  • Department of Medical Laboratory Sciences, Faculty of Health Sciences, Beirut Arab University, Beirut, Lebanon
  • Email
  • Other articles by this author:
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/ Ali Salami
  • Rammal Hassan Rammal Research Laboratory, Physio-toxicity (PhyTox), Lebanese University, Faculty of Sciences (V), Nabatieh, Lebanon
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/ Sophie Visvikis Siest
  • UMR INSERM U1122; IGE-PCV ‘Interactions Gène-Environnement en Physiopathologie Cardiovasculaire’, Université de Lorraine, Nancy, France
  • Department of Internal Medicine and Geriatrics, CHU Technopôle Nancy-Brabois, Vandoeuvre-lès-Nancy, France
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/ Hana M. Fakhoury
  • Corresponding author
  • Department of Biochemistry and Molecular Biology, College of Medicine, Alfaisal University, Riyadh, Kingdom of Saudi Arabia
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/ Rajaa Fakhoury
  • Department of Medical Laboratory Sciences, Faculty of Health Sciences, Beirut Arab University, Beirut, Lebanon
  • Department of Biochemistry and Molecular Biology, College of Medicine, Alfaisal University, Riyadh, Kingdom of Saudi Arabia
  • Other articles by this author:
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Published Online: 2018-02-08 | DOI: https://doi.org/10.1515/dmpt-2017-0030

Abstract

Background

Statin therapy used to lower cholesterol levels results in a substantial reduction in cardiovascular complications. Previous observations in different ethnic populations showed that rs2306283A>G, p.Asn130Asp and rs4149056T>C, p.Val174Ala in solute carrier organic anion transporter 1B1 (SLCO1B1) gene encoding the organic transporter protein may be responsible for statin uptake, thus explaining the majority of statin-associated symptoms. In addition to the genetic component, vitamin D (vit D) deficiency is common in Saudi Arabia and worldwide and may cause muscle dysfunction and ache. The aim of the present study was first to reveal an effect of vit D, rs2306283A>G, and rs4149056T>C and related haplotypes on statin-associated myopathy (SAM) and then to investigate a possible interaction between low vit D levels and the above-mentioned variants.

Methods

The genomic DNA obtained from 50 individuals diagnosed with hypercholesterolemia was genotyped using light SNiP hybridization probes.

Results

Low vit D levels were associated with SAM (OR=3.6, p=0.03); however, CK levels, rs2306283A>G, and rs4149056T>C did not show any association. Interestingly, rs4149056T>C was interacting with vit D to influence SAM (p=0.02). Haplotype analysis showed that SLCO1B1 *1B and *15 were more prevalent in individuals with SAM (p=0.05). When stratified according to vit D levels, rs2306283A allele showed an increase in individuals having SAM along with low vit D (p=0.03).

Conclusions

Although preliminary, our results show an involvement of vit D and rs4149056T>C of SLCO1B1 in SAM.

Keywords: Kingdom of Saudi Arabia; SLCO1B1 gene polymorphisms; statin induced myopathy; vitamin D

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About the article

aBaraa Alghalyini and Said El Shamieh contributed equally to this work.


Received: 2017-10-07

Accepted: 2018-01-04

Published Online: 2018-02-08

Published in Print: 2018-03-28


Author contributions: All the authors have accepted responsibility for the entire content of the submitted manuscript and approved submission.

Research funding: The present work was funded by an internal research grant (project number 0712017) from AlFaisal University, Ryadh, Kingdom of Saudi Arabia.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


Citation Information: Drug Metabolism and Personalized Therapy, Volume 33, Issue 1, Pages 41–47, ISSN (Online) 2363-8915, ISSN (Print) 2363-8907, DOI: https://doi.org/10.1515/dmpt-2017-0030.

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