CYTOCHROME P450 2C19 (CYP2C19) GENOTYPING

DNA ANALYSIS


CYP2C19 is one of the cytochrome P450 enzymes that are responsible for much of Phase I drug metabolism. CYP2C19 metabolizes approximately 15% all prescribed drugs including clopidogrel (Plavix), mephenytoin, diazepam, propranolol, and omeprazole. Genetic variants associated with altered CYP2C19 activities have been identified and are relatively common in most populations. Individuals with two normal activity alleles are referred to as extensive metabolizers. Individuals with two copies of the reduced /non-functional alleles (Poor Metabolizers) have decreased CYP2C19 activity, which may result in adverse drug reactions or decreased drug efficacy. Individuals with one reduced or non-functional allele and one normal activity allele may have intermediate CYP2C19 activity and are referred to as intermediate metabolizers.

The anti-platelet drug clopidogrel (Plavix) is metabolized by CYP2C19 and other enzymes in the liver to an active form. Recent studies indicate that at-risk patients with reduced functional alleles who were treated with clopidogrel had a higher rate of residual platelet aggregation and cardiovascular adverse events.

This analysis tests 10 different variants associated with altered CYP2C19 activity.

Reasons For Referral:

  • Evaluating genetic factors affecting drug metabolism for patients taking drugs metabolized by cytochrome P450 2C19, such as clopidogrel.

Limitations:

  • Not all variants with known impact on enzyme expression and activity are tested in this assay.
  • Non-genetic factors, variations in the other genes involving the drug metabolism are not measured by this assay.
  • Rare genetic alterations at primer binding sites may result in diagnostic errors.

Testing Methodology:

This analysis incorporates DNA amplification by multiplex PCR, allele specific primer extension, microarray hybridization and Fluorescence signal detection.

Variant alleles tested:

  • 2 (c.681G>A)- No activity
  • 3 (c.636G>A)- No activity
  • 4 (c.1A>G)- No activity
  • 5 (c.1297C>T)- No activity
  • 6 (c.395G>A)- No activity
  • 7 (IVS5+2T>A)- No activity
  • 8 (c.358T>C) -No activity
  • 9 (c.431G>A)-Decreased activity
  • 10 (c.680C>T)-Decreased activity
  • 17 (c.-806C>T)-Increased activity

Analytical Sensitivity and Specificity:

Greater than 99%

Specimen Requirements:

Blood: EDTA (purple-top) tubes: Adults: 3cc.
Requisition form must accompany specimen. Prior to any genetic testing, we recommend genetic counseling and request that the subject sign our consent form and submit it with the sample. To receive our forms, additional information, or kits, please contact to our laboratory.

Turnaround Time:

2 weeks

CPT Codes and Prices:

Index: 83891, 83900, 83901x4, 83914x20, 83912

Shipping Information


Forms:

 >> DNA Requisition

References:

  1. Zanger UM, Turpeinen M, Klein K, Schwab M. Functional pharmacogenetics/genomics of human cytochromes P450 involved in drug biotransformation. Anal Bioanal Chem. 2008 Nov; 392(6): 1093-108.

  2. Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT, Walker JR, Antman EM, Macias WL, Braunwald E, Sabatine MS. Cytochrome P450 genetic polymorphisms and the response to prasugrel: relationship to pharmacokinetic, pharmacodynamic, and clinical outcomes. Circulation. 2009 May 19; 119(19): 2553-60.
  3. Simon T, Verstuyft C, Mary-Krause M, Quteineh L, Drouet E, Méneveau N, Steg PG, Ferrières J, Danchin N, Becquemont L; French Registry of Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction (FAST-MI) Investigators. Genetic determinants of response to clopidogrel and cardiovascular events. N Engl J Med. 2009 Jan 22; 360(4): 363-75.

Test Codes:

Index: 6870