Thiopurine methyltransferase

Thiopurine methyltransferase ambar lab

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Most people take it for granted that their body is capable of metabolizing medications or drugs without any problem. And this is true for a large part of the population. But nothing is 100% effective for everyone. We have already talked about the emergence of pharmacogenomics and the wonderful advances it can generate. With a small analysis, drugs can be adjusted to the patient, so that no drug can generate more damage than the organism already suffers due to some incompatibility. There are also other tests that can detect certain deficiencies, such as thiopurine methyltransferase (TPMT).

For this reason, and because the most important thing when it comes to curing any problem is its early detection, we are going to explore this enzyme, how it affects our organism and what is its relationship with the metabolization of certain drugs. Let’s begin!

What is TPMT?

We’ve discussed it before: thiopurine methyltransferase (TPMT for short) is an enzyme, a protein that produces a specific chemical change in all parts of the body. An example of an enzyme action would be blood clotting. These proteins act as catalysts, thereby accelerating the rate at which the body reacts to an external factor. It is the enzymes that intervene when a drug is ingested. They are in charge of breaking it down (metabolizing it) to eliminate it from the organism and at the same time release the effect it may cause.

Among all the types of enzymes we find the protagonist of this post: thiopurine methyltransferase (TPMT). It is responsible for metabolizing a specific type of drugs, known as thiopurines. The function of these drugs, derived from thiopurine, is to suppress the immune system. Examples of thiopurines are azathioprine, mercaptopurine and thioguanine. They are often used in the treatment of various immune or blood disorders. Mercaptopurine and thioguanine are those used to combat leukemia; azathioprine to treat various autoimmune diseases.

Each person is different from another at the DNA level, which means that each person has differences in the genes that code for enzymes. Within the DNA, it is the TPMT gene that indicates how well (or poorly) this enzyme will function in the body. Most of the population has no problem breaking down thiopurines. However, a small percentage can barely metabolize these drugs. If a patient has no TPMT activity, they may experience very serious side effects, such as infection, anemia and bleeding, if they receive a normal dose of a drug containing thiopurines. In these cases, the body without TPMT activity is not able to metabolize the drug. If the drug accumulates in the body, the toxicity levels of the drug cause blood counts to become too low.

Therefore, before starting any treatment it is necessary to test for TPMT enzyme activity or genotype. With this action the physician can make sure that the patient who is going to receive the thiopurinic drug is able to metabolize it.

When should the test be ordered?

Normally, the physician will order a TPMT enzyme activity test or its study at the genetic level when it is known that a patient is going to undergo treatment with a thiopurinic drug. TPMT genotyping is also often requested, although less frequently, when a person already on a thiopurinic drug develops side effects (decreased white blood cell count).

TPMT enzyme activity or TPMT genotyping (which will be explained later) are tests to identify individuals at risk of developing side effects (myelosuppression) from treatment.

The drugs prescribed in case of acute lymphoblastic leukemia, inflammatory bowel disease or some autoimmune diseases are the aforementioned azathioprine, mercaptopurine and thioguanine. Another of its prescriptions is in the case of rejection in recipients of transplanted organs, with the aim of avoiding organ rejection.

What is tested?

About 1 in 300 people are deficient in TPMT. The side effects resulting from this low level of TPMT can lead to very serious diseases, but can be avoided if the ability to produce TPMT is assessed before starting treatment.

To do this, there are 2 ways to test to detect whether a patient may develop side effects from thiopurinic treatment:

  • TPMT enzyme activity. The activity of the enzyme thiopurine S-methyltransferase (TPMT) is measured in blood cells. Depending on the levels, a standard or reduced dose of thiopurine drug or a different drug is prescribed.
  • Genetic study of TPMT. This test identifies variants in the TPMT gene to detect individual genetic differences associated with the risk of thiopurinic toxicity. Everyone has 2 copies of the TPMT gene. Most of the population has these 2 ‘wild-type’ copies. It produces a sufficient amount of the TPMT enzyme for the organism. However, about 10% of the population has one wild-type gene and one gene with an alteration that results in lower TPMT activity and intermediate enzyme activity. One in 300 has both copies altered, resulting in little or no TPMT enzyme activity. Performing a genetic test of this type provides information on how an individual is likely to react to thiopurinic treatment. It does not, however, provide insight into how much TPMT enzyme the body is producing.

Once thiopurinic drug treatment has been started, a third test can be ordered. This will measure the degradation products of thiopurine which allows monitoring of the treatment in order to adjust the dose.

For this test to be performed correctly, it is necessary not to consume TPMT inhibitor drugs at least 48 hours before the determination of TPMT enzyme activity.

What does the result mean?

The results of the TPMT pharmacogenetic test will place the patient in one of these groups:

  • Normal metabolizers. The patient has 2 copies of the normal-functioning TPMT gene, so everything is in order. 9 out of 10 people have this genetic condition. In this case, the dose of thiopurines would be normal.
  • Intermediate metabolizers. There is in the organism a gene of normal function and a copy of a non-functional TPMT gene. In this case, the patient generates a medium TPMT activity, so it may require lower doses of thiopurine drugs to avoid side effects. 1 in 10 people have this condition.
  • Deficient metabolizers. This is the worst case, since there are 2 copies of the non-functional TPMT gene and, in addition, there is no normal TPMT enzyme. The patient therefore suffers a very high risk of experiencing side effects (very low blood counts that could cause life-threatening problems). The patient will have to receive much lower doses than normal. 1 in 300 suffer from this condition.

Do I need to know anything else?

Although TPMT tests predict the risk of developing spinal cord toxicity, blood counts are necessary from time to time to detect this toxicity in patients treated with thiopurinics. A CBC is a common test that measures the number of red blood cells, white blood cells and platelets in the blood. It is often used to monitor treatments that may affect the bone marrow. As the TPMT enzyme activity is measured in red blood cells, its result may be altered if the patient has recently received a blood transfusion.

In addition to genetic predisposition, thiopurinic drugs can produce other risk factors for bone marrow toxicity (myelosuppression). Some of these include naproxen, ibuprofen, ketoprofen, furosemide, sulfasalazine, mesalazine, olsalazine, mefenamic acid, thiazide diuretics, and benzoic acid inhibitors.

There is a possibility that a patient may have elevated levels of TPMT enzyme activity. These may decrease the efficiency of treatment with thiopurinic drugs. In these cases it is recommended to continue treatment with another type of drug.

What is the thiopurine metabolite test?

This test facilitates the monitoring of a thiopurine treatment and allows us to make sure that drug levels in the blood do not reach toxic concentrations.

The enzyme activity or genotype of TPMT is usually assessed before the first dose of drug is administered. The aim of this procedure is to determine the risk of occurrence of undesirable side reactions and to adjust the dose according to the test results. As soon as treatment is started, TPMT metabolites can be measured and monitored. The goal is to adjust (if necessary) the drug dose to avoid toxicity.

What can Ambar Lab do for you?

Thiopurine methyltransferase tests allow you to analyze the TPMT enzyme in order to know in advance how your body will react if you are given certain drugs that affect this enzyme. Thanks to these tests it is possible to know if the normal amount of a drug can have side effects in any patient. From AmbarLabwe know how important this test can be for the health of any person (whether already diagnosed with a disease or not), so ourteam is prepared to perform them and accompany you in all parts of the process, from start to finish. Do you have any questions about this or other tests we perform? You can ask usanything you want either bymailor by phone.

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