PGX CYP3A5 Genotyping

For detection of CYP3A5 variants affecting drug metabolism

Clinical Background

 CYP3A5 encodes a member of the superfamily of enzymes. The cytochrome P450 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 is located on 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 - 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