PGX CYP3A5 Genotyping
For detection of CYP3A5 variants affecting drug metabolism
Clinical Background
CYP3A5 encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. Metabolizer phenotypes can be predicted by the CYP3A5 genotype The clinical impact of the CYP3A5 genotype is influenced by whether a drug is activated or inactivated by CYP3A5, involvement of other metabolic pathways, and other non-genetic factors (eg, other medications, diet). Epidemiology
CYP3A5 variant frequency is ethnicity dependent. Genetics
The CYP3A5 gene is located on chromosome 7q22.1 Inheritance is autosomal recessive. Penetrance is drug-dependent. Indications for Ordering
Pre-therapeutic testing to identify individuals who should avoid, or may require unconventional doses of medications metabolized by CYP3A5. Interpretation
If no CYP3A5 variants are detected, this suggests *1 allele and normal enzymatic activity. If one decreased functional or non-functional CYP3A5 variant is detected, intermediate-to- normal CYP3A5 enzymatic activity is predicted. If two non-functional variants are present on opposite allele, this predicts low CYP3A5 enzymatic activity and a poor metabolizer phenotype. Genotype results should be interpreted in context of the individual clinical situation. Consultation with a clinical pharmacy professional is recommended.
Indiana University School of Medicine Division of Diagnostic Genomics - Pharmacogenomics Laboratory 975 West Walnut Street, IB247 Indianapolis, IN. 46202-5251 Tel. 317-274-0143
Methodology
Realtime Polymerase chain reaction (PCR) and microarray analysis
Variants in CYP3A5 Assay
Allele variant dbSNP Predicted enzyme activity
*1 Assumed when no variant detected normal
*3 c.6986A>G rs28365083 Decreased function
Non-functional or severely *6 c.14690G>A rs10264272 decreased
*7 c.27131_27132insT rs41303343 Decreased function
Indiana University School of Medicine Division of Diagnostic Genomics - Pharmacogenomics Laboratory 975 West Walnut Street, IB247 Indianapolis, IN. 46202-5251 Tel. 317-274-0143