CYP3A5 shares many similarities with CYP3A4. This means that it possibly participates in the clearance of over 50% of clinically used drugs. However, a striking fact related to this enzyme is that many people actually don’t have it. Read on to find more about the gene variants of this enzyme, and how they affect drug metabolism and disease risk.
What is CYP3A5?
CYP3A5 is one of the cytochrome P450 monooxygenases (CYPs). These are enzymes that eliminate most of the drugs and toxins from the human body .
This enzyme is very similar in structure and function to CYP3A4 . However, unlike CYP3A4, it’s activity varies greatly between people, and many actually don’t have a functional version of this enzyme.
The enzyme is functional in most Africans, but in few Whites .
In people who do have this enzyme, it can represent over 50% of the total liver CYP3A activity , contributing greatly to CYP3A metabolism.
This enzyme metabolizes:
- Antihypertensive drugs: felodipine  and nifedipine .
- Immune suppressants: sirolimus , tacrolimus [7, 8] and cyclosporine A .
- Antiemetics: granisetron .
- Anticancer drugs: lapatinib  and vincristine .
- TNF inhibitor etanercept .
- Cholesterol-lowering drugs: simvastatin and atorvastatin 
- Sedatives midazolam and alprazolam (Xanax) .
- Antibiotic erythromycin .
- Antiretroviral drugs: saquinavir .
It plays an important function in the kidneys and may be related to blood pressure .
CYP3A5 The Good
This enzyme can act as a tumor suppressor.
CYP3A5 combats hepatocellular carcinoma (liver cancer). Lower enzyme levels were associated with more aggressive disease, shorter time to disease recurrence after treatment, and worse overall patient survival .
A nonfunctional enzyme variant increased the risk of developing acute and chronic leukemia, emphasizing the significance of effective Phase I detoxification in fighting cancer (144 patients and 241 controls) .
CYP3A5 The Bad
CYP3A5 Gene Polymorphism
There are over 25 variants of this enzyme . Many of them are nonfunctional.
The fully functional variant is known as the CYP3A5*1 .
The frequency of the functional variant is substantially different across ethnic groups. The functional enzyme is found in 45–94% of subjects of African descent, 8–15% of Whites and 23–40% of Asians [15, 2].
People with the functional variant may be more susceptible to salt-sensitive hypertension (elevated blood pressure) (373 and683 subjects) [19, 20]. CYP3A5*1 carriers tend to reabsorb more sodium in the kidneys as they get older .
Enhanced kidney sodium re-absorption could have an advantage in equatorial populations experiencing water shortage by increasing sodium retention. This may explain why this variation is correlated with the geographical distance from the equator .
This is the most common nonfunctional variant of the enzyme, designated as CYP3A5*3 .
Having this variant increases the risk of acute leukemia (ALL), chronic leukemia (CML), and colorectal cancer, especially among Asian and Caucasian populations (meta-analysis, 17 studies, 7,458 cancer patients, and 7,166 controls) .
This is a nonfunctional variant .
Increasing or Decreasing CYP3A5
It is very likely that many of the compounds that increase or decrease CYP3A4 also increase or decrease the CYP3A5 enzyme. However, compared to CYP3A4, a lot less research has been carried out testing CYP3A5. Studies that include this enzyme are listed below.