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SLCO1B1 haplotypes are not associated with atorvastatin-induced myalgia in Brazilian patients with familial hypercholesterolemia

  • Pharmacogenetics
  • Published:
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Abstract

Purpose

Recent studies reported the association of SLCO1B1 haplotypes with the development of musculoskeletal side effects during simvastatin use. The aim was to evaluate the pharmacogenetic association of SLCO1B1 haplotypes with atorvastatin-induced myalgia in a sample of individuals on high-dose atorvastatin regimens.

Methods

One hundred and forty-three patients with familial hypercholesterolemia were followed for at least 12 months while receiving atorvastatin. Genotypes for the rs2306283 (c.A388G) and rs4149056 (c.T521C) polymorphisms were detected by high-resolution melting analysis. These markers form four distinct haplotypes (*1A, *1B, *5 and *15).

Results

During the follow-up period, 14 (9.8%) patients developed myalgia and 16 (11.2%) presented CK levels more than 3 times the upper limit of the normal range. No association of the SLCO1B1 rs2306283 and rs4149056 genotypes or haplotypes with the presence of myalgia or creatine kinase (CK) values was found. Presence of rs2306283 AG + GG genotypes was not associated with increased risks of myalgia or abnormal CK values (OR 2.08, 95% CI 0.62–7.00, p = 0.24 and OR 0.51, 95% CI 0.21–1.26, p = 0.15 respectively). The presence of rs4149056 TC + CC genotypes was also not associated with increased risk of myalgia or abnormal CK values (OR 2.24, 95% CI 0.47–10.72, p = 0.31 and OR 1.51, 95% CI 0.57–3.96, p = 0.41 respectively).

Conclusions

Our findings reaffirm that the SLCO1B1 genetic risk appears to be greater in those patients receiving simvastatin compared with those receiving atorvastatin. This suggests that the importance of SLCO1B1 haplotypes depends on the specific statin that has been used.

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Acknowledgements

PCJL Santos is recipient of a fellowship from FAPESP, Proc. 2010-17465-8, Brazil. We also thank the patients who participated in the study. The technical assistance of the Laboratory of Genetics and Molecular Cardiology group, Heart Institute group is gratefully acknowledged.

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of Sao Paulo Medical School, Avenue Dr. Enéas de Carvalho Aguiar, 44 Cerqueira César, São Paulo, SP, Brazil, CEP 05403-000

    Paulo Caleb Junior Lima Santos, Ana Carolina Moron Gagliardi, Jose Eduardo Krieger & Alexandre Costa Pereira

  2. Lipid Clinic, Heart Institute (InCor), University of Sao Paulo Medical School, São Paulo, SP, Brazil

    Márcio Hiroshi Miname, Ana Paula Chacra & Raul Dias Santos

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  1. Paulo Caleb Junior Lima Santos
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  2. Ana Carolina Moron Gagliardi
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  3. Márcio Hiroshi Miname
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  4. Ana Paula Chacra
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Correspondence to Paulo Caleb Junior Lima Santos or Alexandre Costa Pereira.

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Santos, P.C.J.L., Gagliardi, A.C.M., Miname, M.H. et al. SLCO1B1 haplotypes are not associated with atorvastatin-induced myalgia in Brazilian patients with familial hypercholesterolemia. Eur J Clin Pharmacol 68, 273–279 (2012). https://doi.org/10.1007/s00228-011-1125-1

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