PGX CYP4F2 Genotyping

For detection of CYP4F2 variants affecting drug

Clinical Background

 CYP4F2 encodes a member of the P450 superfamily of . The proteins are which catalyze many reactions involved in drug metabolism and synthesis of , and other .  Metabolizer phenotypes can be predicted by the CYP4F2 genotype  The clinical impact of the CYP4F2 genotype is influenced by whether a drug is activated or inactivated by CYP4F2, involvement of other metabolic pathways, and other non-genetic factors (eg, other , diet). Epidemiology

 CYP4F2 variant frequency is ethnicity dependent. Genetics

 The CYP4F2 gene is located on 19p13.12.  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 CYP4F2. Interpretation

 If no CYP4F2 variants are detected, this suggests *1 allele and normal enzymatic activity.  If one decreased functional or non-functional CYP4F2 variant is detected, intermediate-to- normal CYP4F2 enzymatic activity is predicted.  If two non-functional variants are present on opposite allele, this predicts low CYP4F2 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

Variant in CYP4F2 Assay

Allele variant dbSNP Predicted activity

*1 Assumed when no variant detected Normal

*3 18000G>A rs2108622 Decreased

Indiana University School of Medicine Division of Diagnostic Genomics - Pharmacogenomics Laboratory 975 West Walnut Street, IB247 Indianapolis, IN. 46202-5251 Tel. 317-274-0143