#ExistInterpData>Background Information for Warfarin Genotyping Plus:
Characteristics: Warfarin overdosing can result in life-threatening events, e.g., bleeding. This test does not identify patients at risk for warfarin resistance.
Incidence: Up to 1 percent mortality and 15 percent morbidity due to bleeding complications.
Cause: Mutations in the CYP2C9 and VKORC1 genes. The common CYP2C9 gene mutations (*2 and *3) with the VKORC1 gene promoter mutation (c.-1639G>A), are estimated to account for 40-63 percent of the variability in therapeutic warfarin dose.
Mutations Tested: CYP2C9 *2 (c.430C>T), CYP2C9 *3 (c.1075A>C), VKORC1 (c.-1639G>A).
Allele Frequencies: CYP2C9 *2, 0.08-0.13, 0.02-0.06, and less than 0.01; CYP2C9 *3, 0.06-0.10, less than 0.1, and 0.01-0.04; VKORC1 (c.-1639G>A), 0.42, 0.89, and 0.08 in Caucasian, Asian, and African-American populations, respectively. Other populations are less well characterized. The VKORC1 (c.-1639G>A) is in very strong linkage disequilibrium with the VKORC1 (c.173+1000C>T).
Clinical Sensitivity: 90 percent of CYP2C9 and VKORC1 mutations causing warfarin sensitivity in Caucasians are detected. Less characterized in other populations.
Methodology: Polymerase chain reaction, DNA hybridization, and Electrochemical Detection
Analytical Sensitivity and Specificity: 99 percent.
Limitations: Mutations other than those targeted will not be detected; analytical sensitivity may be compromised by rare primer or probe site mutations.
Counseling and informed consent are recommended for genetic testing. Consent forms are available online at www.aruplab.com.
See Compliance Statement C: www.aruplab.com/CS
||This test generates a customized patient report that provides the clinician with estimated daily and weekly maintenance warfarin doses for the individual patient. However, the following patient information is REQUIRED as input data for the proprietary multivariate mathematical algorithm (PerMIT):
- INR target
- Nicotine use? Y/N
- Amiodarone co-administration? Y/N
- Height in inches
- Weight in pounds
If this patient information is not provided, the Warfarin Sensitivity (CYP2C9 & VKORC1) 3 Mutations (ARUP test code 0051370), which does not have a customized patient report, WILL BE SUBSTITUTED.