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FSOMA<br />

90172<br />

associated with statins is skeletal muscle toxicity, which can include myalgia (with and without elevated<br />

creatine kinase levels), muscle weakness, muscle cramps, myositis, and rhabdomyolysis.(2)<br />

Rhabdomyolysis, while rare, is of clinical concern because of the risk for death as a result of cardiac<br />

arrhythmia, renal failure, and disseminated intravascular coagulation. While the underlying causes of<br />

statin-associated myopathy are not known, several hypotheses have been formulated, including those<br />

related to the biochemical pathway of cholesterol synthesis inhibition and statin metabolism. The<br />

SLCO1B1 *5 (c.521T->C, p.V174A; rs4149056) allele interferes with localization of the transporter to<br />

the plasma membrane, and can lead to increased systemic statin concentrations.(3) All statins are<br />

substrates of OATP1B1, but the association with SLCO1B1 *5 and statin intolerance varies depending on<br />

statin and dose, and is most pronounced with higher doses of simvastatin therapy. A case-control study of<br />

simvastatin-induced myopathy observed an odds ratio (OR) for myopathy of 4.5 per copy of the *5 allele<br />

in patients receiving high-dose (80 mg/day) simvastatin therapy (the OR was 16.9 in *5 homozygotes<br />

compared to individuals who did not carry *5).(4) Also demonstrated was a dose relationship in a<br />

replication cohort of patients taking 40 mg/day simvastatin with a relative risk of 2.6 per copy of the *5<br />

allele. While SLCO1B1 genotype has been shown to affect systemic exposure of other statins (eg,<br />

atorvastatin, pravastatin, rosuvastatin), in addition to simvastatin,(3) there is less evidence demonstrating<br />

a clinical association between SLCO1B1 genotype and myopathy with statins other than simvastatin.(1)<br />

Frequency of the SLCO1B1 *5 allele varies across different racial and ethnic groups. The *5 allele occurs<br />

in the homozygous or heterozygous state in approximately 20% to 28% of Caucasians and Asians, and 8%<br />

of Africans.<br />

Useful For: Aiding prediction of risk for statin-associated myopathy for patients beginning statin<br />

therapy, especially simvastatin therapy Determining a potential genetic effect related to statin intolerance<br />

in patients with statin-associated myopathy, especially related to simvastatin Assessing the SLCO1B1 *5<br />

genotype in patients who received a blood transfusion or bone marrow transplant in the preceding 45 days<br />

(6 weeks)<br />

Interpretation: Heterozygosity and homozygosity for the SLCO1B1 *5 allele is associated with<br />

decreased OATP1B1 activity and an increased risk for simvastatin-associated myopathy. Absence of the<br />

SLCO1B1 *5 allele decreases, but does not rule-out entirely, the risk of simvastatin-associated myopathy.<br />

Reference Values:<br />

An interpretive report will be provided.<br />

Clinical References: 1. Wilke RA, Ramsey LB, Johnson SG, et al: The Clinical pharmacogenomics<br />

Implementation Consortium: CPIC guideline for SLCO1B1 and simvastatin-induced myopathy. Clin<br />

Pharmacol Ther 2012. Epub ahead of print 2. Wilke RA, Lin DW, Roden DM, et al: Identifying genetic<br />

risk factors for serious adverse drug reactions: current progress and challenges. Nat Rev Drug Discov<br />

2007;6(11):904-916 3. Niemi M: Transporter pharmacogenetics and statin toxicity. Clin Pharmacol Ther<br />

2012;87:130-133 4. Link E, Parish S, Armitage J, et al: SLCO1B1 variants and statin-induced myopathy-a<br />

genomewide study. N Engl J Med 2008 Aug 21;359(8):789-799<br />

Somatostatin<br />

Clinical Information: Somatostatin is a cyclic peptide originally isolated from sheep hypothalami<br />

and shown to inhibit the release of Growth Hormone. Somatostatin is present primarily in three main<br />

forms: a 14 amino acid peptide, a 28 amino acid peptide (Big Somatostatin), and a 12,000 molecular<br />

weight Pro-Somatostatin. This assay measures only the 14 amino acid form of Somatostatin. All three<br />

forms of Somatostatin have similar biological properties and overall potencies. Somatostatin is a<br />

physiological regulator of islet cell and gastrointestinal functions, and is a suppressor of many pituitary<br />

hormones including Growth Hormone, Prolactin, and Thyrotropin (TSH). Somatostatin levels are often<br />

elevated in diabetics, but the levels return to normal upon correction of the hormonal and metabolic<br />

deficiencies present. In many cases of APUDomas including VIPoma, Insulinoma, Glucagonoma, and<br />

Gastrinoma, elevated levels of Somatostatin are found.<br />

Reference Values:<br />

Up to 25 pg/ml<br />

Current as of January 4, 2013 7:15 pm CST 800-533-1710 or 507-266-5700 or <strong>Mayo</strong><strong>Medical</strong><strong>Laboratories</strong>.com Page 1608

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