Pharmacogenomic Testing References

The PGx Mental Health (MH) test analyses a specific group of genes that are known to be involved in drug metabolism for a broad range of medications used in the treatment of mental health conditions. The report provides detailed interpretation and prescribing recommendations for many antidepressants, antipsychotics, ADHD medications and some anxiolytics, all of which are listed in the Pharmacogenomics Medication List, downloadable at the bottom of the page.

The PGx Pain test analyses a specific group of genes that are known to affect the drug response to several analgesics used to treat different types of pain. The report provides detailed interpretation and prescribing recommendations for several opioid analgesics, non-steroidal anti-inflammatory drugs (NSAIDs) and some medications used for neuropathic pain, all of which are listed in the Pharmacogenomics Medication List downloadable at the bottom of the page.

Thiopurine drugs are used as both immunosuppressive and chemotherapeutic agents. Inherited genetic variants that result in reduced activity of the enzyme thiopurine S-methyltransferase (TPMT) are associated with cytoxicity and particularly with bone marrow failure. Multiple variants have been associated with decreased TPMT activity but 4 specific variant alleles (TPMT*2, TPMT*3A, TPMT*3B and TPMT*3C), account for the majority (>95%) of low and intermediate activity cases. Patients with one variant allele have intermediate activity whereas those with two variants have low or no activity.

TPMT genetic testing can predict thiopurine drug toxicity in a variety of conditions, including renal transplantation, rheumatoid disease, inflammatory bowel disease and lymphoblastic leukaemia. Genetic variants have also been implicated in ototoxicity associated with cisplatin treatment in children.

Gilbert’s syndrome is characterised by jaundice due to increased levels of unconjugated plasma bilirubin. Men are at higher risk than females and usually present post-puberty. In people of northern European ancestry, cases of Gilbert’s syndrome are often associated with inheriting two copies (one from each parent) of a specific mutation in the promoter region of the gene encoding the enzyme glucuronyltransferase (UGT1A1), designated UGT1A1*28 allele. UGT1A1 is a liver enzyme important for clearing conjugated bilirubin from the circulation. In general, other than the low grade elevated bilirubin levels, people with Gilbert’s syndrome exhibit no other signs or symptoms. In some cases, toxicity therapeutic agents, such as anticancer agent irinotecan and anti-viral protease inhibitor Indinivar, may occur in patients with Gilbert’s syndrome.

Testing for Gilbert’s syndrome may assist in differentiating the cause of isolated elevated bilirubin levels in those patients with normal test results for FBC, reticulocytes, haptoglobin and liver enzymes.