title: Physiogenomic analysis links serum creatine kinase activities during statin therapy to vascular smooth muscle homeostasis.
abstract: Statins are highly effective at reducing coronary disease risk. The main side effects of these medications are a variety of skeletal muscle complaints ranging from mild myalgia to frank rhabdomyolysis. To search for physiologic factors possibly influencing statin muscle toxicity, we screened for genetic associations with serum creatine kinase (CK) levels in 102 patients receiving statin therapy for hypercholesteremia. A total of 19 single nucleotide polymorphism (SNPs) were selected from ten candidate genes involved in vascular homeostasis. Multiple linear regression was used to rank the SNPs according to probability of association, and the most significant associations were analyzed in greater detail. SNPs in the angiotensin II Type 1 receptor (AGTR1) and nitric oxide synthase 3 (NOS3) genes were significantly associated with CK activity. These results demonstrate a strong association between CK activity during statin treatment and variability in genes related to vascular function, and suggest that vascular smooth muscle function may contribute to the muscle side effects of statins.
authors.affiliation: Genomas, Inc., 67 Jefferson St., Hartford, CT 06106, USA. g.ruano@genomas.net
authors.forename: Gualberto
authors.initials: G
authors.lastname: Ruaño
authors.forename: Paul D
authors.initials: PD
authors.lastname: Thompson
authors.forename: Andreas
authors.initials: A
authors.lastname: Windemuth
authors.forename: Andrew
authors.initials: A
authors.lastname: Smith
authors.forename: Mohan
authors.initials: M
authors.lastname: Kocherla
authors.forename: Theodore R
authors.initials: TR
authors.lastname: Holford
authors.forename: Richard
authors.initials: R
authors.lastname: Seip
authors.forename: Alan Hb
authors.initials: AH
authors.lastname: Wu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D003402:Creatine Kinase / Q000235:genetics* / Q000502:physiology*; D003627:Data Interpretation, Statistical; D005260:Female; D005838:Genotype; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009131:Muscle, Smooth, Vascular / Q000201:enzymology* / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D003402:Creatine Kinase