Low Vitamin D Levels and Genetic Polymorphism in the Vitamin D Receptor are Associated with Increased Risk of Statin-Induced Myopathy

Basic Clin Pharmacol Toxicol. 2016 Mar;118(3):214-8. doi: 10.1111/bcpt.12482. Epub 2015 Oct 1.

Abstract

The main aim of this study was to test the hypothesis whether 25-hydroxyvitamin D (25OHD) levels <50 nmol/L at baseline could predict statin-induced myopathy during the course of treatment. In addition, we analysed the association between a genetic polymorphism in the vitamin D receptor (VDR) and the risk of statin-induced myopathy. We used serum samples from a prospective, observational study in statin-treated patients in Sweden who were thoroughly followed with interviews and questionnaires regarding muscular symptoms (n = 127). In this cohort, 16 developed muscular symptoms and 111 had no muscular symptoms associated with statin treatment during the first year of follow-up. Patients with 25OHD levels <50 nmol/L before starting on statin treatment had four times higher risk of developing muscular symptoms compared with individuals having 25OHD levels >50 nmol/L (RR 4.2; 95% CI 1.7-10.2; p < 0.01). The mean levels of 25OHD at baseline were 50 ± 4 nmol/L among patients developing myopathy and 60 ± 2 nmol/L among patients without myopathy (p < 0.01). Individuals homozygous for the C allele in the VDR polymorphism TaqI (rs731236) had a four times higher risk of developing muscular symptoms; (RR 4.37, 95% CI 1.9-10.1, p < 0.01). In conclusion, 25OHD levels <50 nmol/L might be a useful marker to predict muscular adverse events during statin treatment. In addition, the finding that the VDR polymorphism TaqI was associated with myopathy may indicate a causal relationship between vitamin D function and myopathy, but larger studies are needed before firm conclusions can be drawn.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Biomarkers / blood
  • Female
  • Follow-Up Studies
  • Genotyping Techniques
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects*
  • Male
  • Middle Aged
  • Muscular Diseases / blood*
  • Muscular Diseases / chemically induced
  • Observational Studies as Topic
  • Polymorphism, Genetic*
  • Receptors, Calcitriol / genetics*
  • Risk Factors
  • Vitamin D / blood
  • Vitamin D Deficiency / blood*
  • Vitamin D Deficiency / complications
  • Vitamin D Deficiency / genetics*

Substances

  • Biomarkers
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Receptors, Calcitriol
  • Vitamin D