title: Low Vitamin D Levels and Genetic Polymorphism in the Vitamin D Receptor are Associated with Increased Risk of Statin-Induced Myopathy.
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.
authors.affiliation: Division of Clinical Pharmacology, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Ovesjö
authors.affiliation: Division of Clinical Pharmacology, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
authors.forename: Ilona
authors.initials: I
authors.lastname: Skilving
authors.affiliation: Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Bergman
authors.affiliation: Division of Clinical Pharmacology, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Rane
authors.affiliation: Division of Clinical Pharmacology, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
authors.forename: Lena
authors.initials: L
authors.lastname: Ekström
authors.affiliation: Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
authors.forename: Linda
authors.initials: L
authors.lastname: Björkhem-Bergman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D015415:Biomarkers / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D060005:Genotyping Techniques; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009135:Muscular Diseases / Q000097:blood* / Q000139:chemically induced; D064887:Observational Studies as Topic; D011110:Polymorphism, Genetic; D018167:Receptors, Calcitriol / Q000235:genetics*; D012307:Risk Factors; D014807:Vitamin D / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood* / Q000150:complications / Q000235:genetics*
chemical_list: D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018167:Receptors, Calcitriol; D014807:Vitamin D