Tacrolimus metabolism (CYP3A5 gene)

The CYP3A5 enzyme breaks down the transplant drug tacrolimus. Whether your body makes this enzyme sets how much drug you need, and many people of European descent make little or none of it.

Possible results

Fast tacrolimus metabolism. You make the CYP3A5 enzyme (the normal type), which breaks down the transplant drug tacrolimus. People who make it clear the drug quickly, so they usually need a higher dose. This only matters if you ever take tacrolimus.

Intermediate tacrolimus metabolism. You carry one working copy and one non-working copy of CYP3A5. You still make some of the enzyme that clears the transplant drug tacrolimus, so you'd fall in an intermediate dosing range. Relevant only in a transplant setting.

Slow tacrolimus metabolism. You carry the non-working version of CYP3A5, so you make little or none of the enzyme, which is common in people of European descent. You clear the transplant drug tacrolimus slowly, so standard dosing usually fits. This only comes into play if you ever need tacrolimus.

Evidence & sources

Across global populations, about 80% of people carry two copies of this variant, and about 4% carry none.

CPIC provides dosing guidance for tacrolimus based on this gene.

This variant appears in 9 published genetic studies: PubMed 30801552 · PubMed 31959995 · PubMed 33755393 · PubMed 35977080 · PubMed 36357675 · PubMed 36635386 · PubMed 37277652 · PubMed 37524825 · PubMed 39644095.

Related

Abacavir hypersensitivity (HLA-B*57:01) · CYP2C19 metabolizer status (clopidogrel & others) · Drug acetylation speed (NAT2) · Efavirenz / drug metabolism (CYP2B6*6) · Fluoropyrimidine (5-FU) toxicity risk · Gilbert syndrome (UGT1A1 gene) · Opioid receptor response (OPRM1 A118G)