PHARMACOGENOMICS (PGx)

Infectious Disease PGx Panel
Test description

This test is for individuals with a clinical diagnosis of long QT syndrome (LQTS). The primary Invitae Long QT Syndrome panel includes genes that are definitively associated with LQTS or other inherited arrhythmia disorders that may present with clinical features similar to LQTS. Individuals with clinical symptoms of LQTS may benefit from diagnostic genetic testing to establish or confirm diagnosis, clarify risks, or inform management. Asymptomatic members of a family with a known LQTS pathogenic variant may also benefit by avoiding activities and medications that can trigger symptoms.

Patient (Consult a Provider)
Patient (Order a Kit)
Provider
Ordering information

Turnaround Time: 3-7 business days
Preferred speciment: Saliva
Alternate specimens: Buccal Swab

Testing Kit Request Form

Clinical description

Many medications used to treat infectious diseases are metabolized by liver enzymes including CYP2C19. Trough voriconazole concentrations found to be lower in patients with CYP2C19 ultra-rapid metabolizers compared to poor metabolizers resulting in delay in achieving therapeutic level. This may be critical in life-threatening infections such as invasive aspergillosis. CPIC guideline recommends that patients with CYP2C19 ultra-rapid or rapid metabolizer status to receive an alternative agent other than voriconazole as therapeutic level may not be achievable. Patients with CYP2C19 poor metabolizer status should use an alternative agent due to high risk for developing adverse effects.
It is well described that HLA-B*5701 screening reduces the risk of hypersensitivity reaction to abacavir.

Infectious Disease PGx Test Panel
HLA-B*5701, CYP2C19, CYP2B6, CYP3A4

Many medications used to treat infectious diseases are metabolized by liver enzymes including CYP2C19. Trough voriconazole concentrations found to be lower in patients with CYP2C19 ultra-rapid metabolizers compared to poor metabolizers resulting in delay in achieving therapeutic level. This may be critical in life-threatening infections such as invasive aspergillosis. CPIC guideline recommends that patients with CYP2C19 ultra-rapid or rapid metabolizer status to receive an alternative agent other than voriconazole as therapeutic level may not be achievable. Patients with CYP2C19 poor metabolizer status should use an alternative agent due to high risk for developing adverse effects.
It is well described that HLA-B*5701 screening reduces the risk of hypersensitivity reaction to abacavir.

Medication Gene
Abacavir HLA-B*5701
Voriconazole CYP2C19
Nevirapine, Efavirenz CYP2B6
Ketoconazole CYP3A4

Frequency of Cytochrome P450 (CYP2C19) Metabolizer Types in the population
Cytochrome Poor metabolizer Intermediate metabolizer Normal metabolizer Rapid or ultra-rapid metabolizer
CYP2C19 2-20% 24-36% 14-44% 30%
Tagged Genes

Primary panel:

4 genes selected

References
  • Evans WE, McLeod HL. Pharmacogenomics—drug disposition, drug targets, and side effects. N Engl J Med. 2003;348(6):538–549.
  • Johnson JA, Cavallari LH. Pharmacogenetics and cardiovascular disease: implications for personalized medicine. Pharmacol Rev. 2013;65(3):987–1009.
  • Cavallari LH, Lee CR, Beitelshees AL, et al. Multisite investigation of outcomes with implementation of CYP2C19 genotype-guided antiplatelet therapy after percutaneous coronary intervention. JACC Cardiovasc Interv. 2018;11(2):181–191. doi:10.1016/j.jcin.2017.07.022
  • Jneid H, Anderson JL, Wright RS, et al. 2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/non–ST-elevation myocardial infarction. Circulation. 2012;126(7):875–910. doi:10.1161/CIR.0b013e318256f1e0
  • Scott SA, Sangkuhl K, Stein CM, et al. Clinical Pharmacogenetics Implementation Consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 update. Clin Pharmacol Ther. 2013;94(3):317–323. doi:10.1038/clpt.2013.105
  • Johnson JA, Caudle KE, Gong L, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for pharmacogenetics-guided warfarin dosing: 2017 update. Clin Pharmacol Ther. 2017.
  • Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) Collaborative Group. Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomised trial. Lancet. 2010;376(9753):1658–1669. doi:10.1016/S0140-6736(10)60310-8
  • The SEARCH Collaborative Group. SLCO1B1 variants and statin-induced myopathy—a genomewide study. N Engl J Med. 2008;359(8):789–799. doi:10.1056/NEJMoa0801936
  • Clinical Pharmacogenetics Implementation Consortium (CPIC). Genes–drug pairs. https://cpicpgx.org/genes-drugs
  • U.S. Food and Drug Administration. Table of pharmacogenomic biomarkers in drug labeling. https://www.fda.gov/drugs/science-and-research-drugs/table-pharmacogenomic-biomarkers-drug-labeling