The science behind the Boston Heart Statin Induced Myopathy (SLCO1B1) Genotype test

Statins have been shown to significantly reduce heart attack and related event rates by more than 30%, yet patient compliance remains a significant problem. Studies estimate that up to 50% of patients with cardiovascular disease stop taking their statin medications as directed. Many do so because of statin associated muscle symptoms (SAMS)—the onset of muscle aches, spasms, weakness and/or pain associated with statin therapy. 60% of people who stopped taking a statin cited muscle pain as the primary reason.1 Muscle complications are considered to be the most frequent adverse events associated with all statins and this leads many to forego taking these potentially life-saving drugs.1,2

An association has been established between statin induced myopathy and variations in the SLCO1B1 gene.

The SLCO1B1 (Solute Carrier Organic Anion Transporter 1B1) gene codes for the organic anion transporter 1B1 responsible for the liver’s uptake and metabolism of statins. Inherited variations in the SLCO1B1 gene known as SNPs (single nucleotide polymorphisms) affect the function of this transporter.3 The presence of this common variant to SLCO1B1 results in a significantly decreased ability to take up statins by the liver, less effectiveness of the statin in lowering ‘bad’ LDL cholesterol levels, higher blood levels after dosing, and an increased risk of myopathy. Studies show that people who have inherited one or two copies of a specific SLCO1B1 variant are up to 4.5-fold and 17-fold increased risk respectively for developing significant myopathy due to statins.4-6

SLCO1B1 Genotype Predicts Ability to Metabolize Statins

Three SLCO1B1 genotypes have been identified and classified in terms of their effect on statin metabolism in the liver—normal (T/T), decreased (T/C), and markedly decreased (C/C):

    • The T/T genotype (valine/valine) is classified as normal statin metabolizers. These patients have a normal ability to metabolize statins (about 75% of the population). Standard doses of statins, if indicated, are recommended for LDL-C lowering.
    • The T/C genotype (valine/alanine) is classified as a decreased statin metabolizer. These patients have a decreased ability to metabolize statins (about 23% of the population). They have up to a 4.5-fold increased risk for developing statin induced myopathy.
    • The C/C genotype (alanine/alanine) is classified as a markedly decreased statin metabolizer. These patients have a significantly decreased ability to metabolize statins (about 2% of the population). They have up to a 17-fold increased risk of developing myopathy on statin therapy.

Additionally, individuals carrying the T/C or C/C genotype are less responsive to statins for LDL-C lowering than those carrying the T/T genotype.

Carriers of the SLCO1B1*5 allele (Val174Ala, rs4149056) are at 2-fold relative risk of mild statin induced side effects, the majority of which had normal CK levels. These results could have potential implications for clinical practice because the vast majority of patients who are intolerant of statin have mild symptoms without CK elevations.
- Voora, American Cardiology (2009)3

SLCO1B1 Genotyping Using this Exclusive Assay

The Boston Heart Statin Induced Myopathy (SLCO1B1) Genotype test uses real-time polymerase chain reaction (PCR) to identify genetic variants (SNPs) on the SLCO1B1 gene. The three identified genotypes—normal (T/T), decreased (T/C), and markedly decreased (C/C)—can be detected.

The genotyping of SLCO1B1 polymorphisms may be useful in the future for tailoring both the statin dose and safety monitoring (especially when statins are used in combination with certain other drugs and during the first year of treatment, when the absolute risk of myopathy is greatest) in order to obtain the benefits of statin therapy more safely and effectively.
- The SEARCH Collaborative Group (2008)6

Optimize Patient Management & Treatment Strategies

SLCO1B1 genotyping is another example of how Boston Heart is helping to fulfill the promise of personalized medicine. These results help healthcare providers identify those patients who are at higher risk for statin induced myopathy due to a variation in their SLCO1B1 gene, and prescribe the right statin type and dose with the least probability of causing myopathy accordingly.

The benefits of SLCO1B1 genotyping are:

    • Advanced identification of those patients who are at higher risk for statin induced myopathy due to:
      • Reduced ability to metabolize statins.
      • Higher blood levels after dosing.
    • Ability to prescribe the right drug type in the right dose according to a patient’s identified SLCO1B1 genotype.
      • For patients with the T/C or C/C genotypes, healthcare providers should consider using lower doses of water-soluble statins. Combination therapy including ezetimibe or colesevelam to augment LDL-C lowering response if needed should also be considered.
    • Reduced time and expense in achieving optimal therapeutic outcomes.
    • Other factors associated with risk of statin induced myopathy include:
      • Clinical Conditions
        • Diabetes
        • Creatine >1.0 mg/dL
        • Hypothyroidism
        • Use of calcium channel blockers
        • Use of amiodorone
      • Other Causes:
        • Age >65 years
        • Female gender
        • Physical activity

1. Wei MY, Ito MK, Cohen JD, Brinton EA, Jacobson TA. Predictors of statin adherence, switching, and discontinuation in the USAGE survey: Understanding the use of statins in America and gaps in patient education. J Clin Lipidol. 2013;7(5):472-483.
2. Stroes ES, Thompson PD, Corsini A, et al. Statin-associated muscle symptoms: impact on statin therapy—European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management. Eur Heart J. 2015;36(17):1012-1022.
3. Voora D, Shah SH, Spasojevic I, Ali S, Reed CR, Salisbury BA, Ginsburg GS. The SLCO1B1*5 genetic variant is associated with statin-induced side effects. J Am Coll Cardiol 2009;54:1609–1616.
4. Akao H, Polisecki E, Kajinami K, Trompet S, Robertson M, Ford I, Jukema JW, de Craen AJ, Westendorp RG, Shepherd J, Packard C, Buckley BM, Schaefer EJ. Genetic Variation at the SLCO1B1 Gene Locus and Low Density Lipoprotein Cholesterol Lowering Response to Pravastatin in the Elderly. Atherosclerosis 2012;220(2):413-417.
5. Boston Heart Diagnostics. Database of over 250,000 samples.
6. The SEARCH Collaborative Group. SLCO1B1 variants and statin-induced myopathy – a genomewide study. N Engl J Med. 2008;359:789–799.

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