CPT Code(s): 81226 (CYP2D6), 81230 (CYP3A4), 81231 (CYP3A5)
Service Code (IU Health): 8618406557
Ordering Recommendation: Information about genotype may be used as an aid to clinicians in determining therapeutic strategy for individuals undergoing heart transplantation.
Synonyms: CYP2C19, CYP2D6, CYP3A4, CYP3A5, heart transplant, voriconazole, tacrolimus, pain, opioids
Methodology: Real-time polymerase chain reaction (PCR) and hydrolysis probe analysis
Performed: Weekly
Reported: 7-10 days
Patient Preparation: Whole blood: none required; Saliva: no eating, drinking, smoking or chewing gum 30 minutes prior to collection
Collect: Preferred: Lavender (EDTA); Acceptable: Yellow (ACD Solution A or B), Green (Heparin), Saliva (Oragene collection device)
Specimen Volume: Blood: 3 mL whole blood (minimum 1 mL); Saliva: 2 mL
Storage/Transport: Refrigerated/Room temperature
Unacceptable Conditions: Grossly hemolyzed or clotted
Stability: One month refrigerated; One month frozen
Reference Interval: by report
Characteristics: Patients undergoing kidney, heart, lung, or hematopoietic stem cell transplant are often prescribed tacrolimus. Blood concentrations of tacrolimus are strongly influenced by CYP3A5 genotype, with substantial evidence linking CYP3A5 genotype with phenotypic variability. Individuals with a normal or intermediate metabolizer phenotype will generally require an increased dose of tacrolimus to achieve therapeutic drug concentrations.
Inheritance: Autosomal recessive
Cause: CYP2C19, CYP2D6, CYP3A4, and CYP3A5 allelic variants
Penetrance: Drug dependent
Clinical sensitivity: Unknown
Analytical sensitivity and specificity: 99%
Limitations: Only the targeted variants will be detected. Mutations or variants in other genes will not be detected. Although rare, false positive or false negative results may occur. All results should be interpreted in the context of clinical findings, relevant history, and other laboratory data.
References:
Variants Tested
| Allele | Variant | dbSNP | Predicted enzyme activity |
|---|---|---|---|
| *1 | Assumed when no variant detected1 | Normal function | |
| CYP2C19*2 |
c.681G>A |
rs4244285 |
No function |
| CYP2C19*3 |
c.636G>A |
rs4986893 |
No function |
| CYP2C19*4 |
c.1A>G |
rs28399504 |
No function |
| CYP2C19*6 |
c.395G>A |
rs72552267 |
No function |
| CYP2C19*8 |
c.358T>C |
rs41291556 |
No function |
| CYP2C19*17 (also *4 haplotype [*4B]) |
c.-806C>T |
rs12248560 |
Increased function |
| CYP2D6*2 |
2851C>T 4181G>C |
rs16947 rs1135840 |
Normal function |
| CYP2D6*3 |
2550delA |
rs35742686 |
No function |
| CYP2D6*4 |
1847G>A 100C>T |
rs3892097 rs1065852 |
No function |
| CYP2D6*5 |
CYP2D6 deleted |
No function |
|
| CYP2D6*6 |
1707delT |
rs5030655 |
No function |
| CYP2D6*7 |
2936A>C |
rs5030867 |
No function |
| CYP2D6*8 |
1759G>T |
rs5030865 |
No function |
| CYP2D6*9 |
2615delAAG |
rs5030656 |
Decreased function |
| CYP2D6*10 |
100C>T 4181G>C |
rs1065852 rs1135840 |
Decreased function |
| CYP2D6*17 |
1022C>T 2851C>T |
rs28371706 rs16947 |
Decreased function |
| CYP2D6*29 |
1660G>A 2851C>T 3184G>A 4181G>C |
rs61736512 rs16947 rs59421388 rs1135840 |
Decreased function |
| CYP2D6*41 |
2989G>A 2851C>T 4181G>C |
rs28371725 rs16947 rs1135840 |
Decreased function |
| CYP2D6*1XN |
Duplication |
Increased function |
|
| CYP2D6*2XN |
Duplication |
Increased function |
|
| CYP2D6*4XN |
Duplication |
No function |
|
| CYP2D6*6XN |
Duplication |
No function |
|
| CYP2D6*9XN |
Duplication |
Normal function |
|
| CYP2D6*17XN |
Duplication |
Normal function |
|
| CYP2D6*29XN |
Duplication |
Normal function |
|
| CYP2D6*41XN |
Duplication |
Normal function |
|
| CYP3A4*2 |
g.15713T>C |
rs55785340 |
Decreased function |
| CYP3A4*22 |
c.15389C>T |
rs35599367 |
Decreased function |
| CYP3A5*3 |
c.6986A>G |
rs28365083 |
Decreased function |
| CYP3A5*6 |
c.14690G>A |
rs10264272 |
No function or severely decreased function |
| CYP3A5*7 |
c.27131_27132insT |
rs41303343 |
Decreased function |
1*1 is reported when no variant is detected for the following genes: CYP2D6, CYP3A4, and CYP3A5