1. An Electronic Medical Record Based Pharmacogenetic Study
Association of a Polymorphism in SLCO1B1 with Statin-Induced Myalgias, Myositis and Myopathy-
An Electronic Medical Record Based Pharmacogenetic Study
Adnan A Khan, MD, Keyue Ding, PhD, Khader Shameer, Iftikhar J Kullo, MD.
Division of Cardiovascular Diseases
Mayo Clinic, Rochester, MN
BACKGROUND
Solute Carrier Organic anion transporter family member 1B1 (SLCO1B1) - an important pharmacogene, encodes a transmembrane receptor involved in hepatic drug transport. We investigated the association of genotypes (CC, CT and TT) at a non-synonymous SNP (rs , minor allele frequency = 0.16) in SLCO1B1 with statin induced myalgias/myositis/myopathy by leveraging an electronic medical record (EMR)-based genome-wide association study (GWAS)
RESULTS
Myalgia was defined as unexplained new muscle pain, tenderness or weakness, myositis as myalgias with elevated serum creatinine kinase (CK) (men >336 u/L, women >176 u/L), and myopathy as CK 10 times above the upper limits of normal.
Statin related adverse events were present in 10 CC (15.6 %), 6 CT (9.3%) and 3 TT (4.6%) patients (P=0.07, Fisher’s exact test).
7 (70%) of CC genotype patients were able to tolerate another brand of statin as compared to 5 (83.3%) of CT genotype. None of patients in TT genotype were able to tolerate any brand name statin.
Figure 3: Statin Tolerance
METHODS
Of 3336 whites (63±9 y, 62% men) genotyped on the Illumina 660W platform for a GWAS of peripheral arterial disease, 87 patients had the CC genotype and 64 of these were on statins. We randomly chose an equal number of age and sex-matched individuals on statins from 877 CT and 2372 TT patients and reviewed the EMR of these patients for presence of statin-related adverse effects
CONCLUSIONS
Presence of the C allele at rs in SLCO1B1 is associated with increased risk of adverse reactions to statin therapy and knowledge of this allele may improve prediction of adverse reactions to such therapy.
TT genotypes have fewer and milder forms of statin related adverse reactions yet patients with such genotype are unlikely to tolerate another statins in future due to reoccurrence of myalgias with statin therapy.
Our results highlight the potential clinical utility of EMR-based pharmacogenetic studies.
Patients tolerating same or another brand name statin with CC, CT, TT genotypes.
Figure 2: Muscle related side effects
Figure 1: SLCO1B1 Gene
REFERENCES
1. Group SC, Link E, Parish S, et al. SLCO1B1 variants and statin-induced myopathy--a genomewide study. New England Journal of Medicine 2008;359:
2. Voora D, Shah SH, Spasojevic I, et al. The SLCO1B1*5 genetic variant is associated with statin-induced side effects. Journal of the American College of Cardiology 2009;54:
3. Oshiro C, Mangravite L, Klein T, Altman R. PharmGKB very important pharmacogene: SLCO1B1. Pharmacogenetics and Genomics 2010;20:211-6.
CC, CT, TT genotypes at non-synonymous SNP rs
Figure legend Location of SNP rs mapped on the homology model of SLCO1B1, model is generated using SWISSMODEL server using the template structure 2CFQ (Sequence identity: 8%) .