TPMT Antibodies

Thiopurine S-methyltransferase (TPMT)

Catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine (also referred to as mercaptopurine, 6-MP or its brand name Purinethol) and 6-thioguanine (also referred to as tioguanine or 6- TG) using S-adenosyl-L-methionine as the methyl donor (PubMed:657528, PubMed:18484748). TPMT activity modulates the cytotoxic effects of thiopurine prodrugs.

A natural substrate for this enzyme has not yet been identified. .

Gene Information

Human
Gene Name:	TPMT
Uniprot:	P51580
Entrez:	7172

Family

Belongs to:
class I-like SAM-binding methyltransferase superfamily

Alternative Names

EC 2.1.1.67; S-adenosyl-L-methionine:thiopurine S-methyltransferase; Thiopurine methyltransferase; thiopurine S-methyltransferase

Molecular Weight

Mass (kDA):
28.18 kDA

Genomic Context

Human
Location:	6p22.3
Sequence:	6; NC_000006.12 (18128311..18155169, complement)

Subcellular Localizations

Cytoplasm.

Diseases

• Inflammatory Bowel Diseases
• Leukemia
• Intestinal Diseases
• Acute Lymphocytic Leukemia
• Crohn Disease
• Thiopurine S Methyltranferase Deficiency
• Leukopenia
• Malignant Neoplasms
• Ulcerative Colitis
• Medication Reaction
• Autoimmune Reaction
• Neoplasms

• Colitis
• Ulcer
• Hepatotoxicity
• Autoimmune Diseases
• Pancytopenia
• L1 Acute Lymphoblastic Leukemia
• Rheumatoid Arthritis

Pathways

• Methylation
• Transport
• Translation
• Conjugation
• Proteolysis
• Hypersensitivity
• Excretion
• Autophagy
• Drug Transport
• Pathogenesis
• Programmed Cell Death
• Defecation Rhythm
• Dna Repair

• Dna Methylation
• Response To Drug
• Cell Division
• Drug Resistance
• Dna Amplification
• Fermentation
• Cell Cycle

PTMs

• Methylation
• Reduction
• Phosphorylation

• Cleavage
• Acetylation
• Oxidation

For details, visit:
bosterbio.com/bosterbio-gene-info-cards/TPMT

Best Uses Of The TPMT Marker

There are several factors you should consider when searching for the best TPMT antibody. TPMT antibodies are highly specific and can detect any variants of TPMT. They can also detect bone-marrow toxicities. Here are some of the benefits of TPMT antibodies. We hope you will find them helpful! Continue reading to learn even more.

TPMT Test detects most variants associated with TPMT Deficiency

TPMT deficiency is an autosomal recessive disorder that causes the synthesis of thymine. Approximately one in 300 people have the disease. The most common variant, *2/*3A is the most common. This is more common among African-Americans and European Caucasians that it is among blacks. TPMT activity is 50% greater in newborn infants than in race-matched adults. The activity in newborn infants resembles that in Korean schoolchildren. Adult TPMT activity is similar with that found in newborn infants. However it is not yet fully characterized.

Allele-specific and RFLP are the most popular methods of identifying TPMT variations. The most popular technique is RFLP. It involves individual PCR reactions. It is however time-consuming and resource-intensive. Therefore, a TPMT test detects the most common variants associated with TPMT deficiency.

Despite this, TPMT gene mutations can be found in many forms. TPMT genotypes tend to be associated with good activity. However, there can be significant differences between genotype and phenotype that can only been detected with a TPMT assay. If you suspect that you might have TPMT deficiency the TPMT test could be a good option.

The red blood cells measure the TPMT enzyme activities. Recent blood transfusions, genetic makeup and thiopurine medication treatment can all impact TPMT's enzyme activity. Certain drugs inhibit TPMT enzyme activity, including naproxen, thiazide diuretics, and benzoic acid inhibitors. Therefore, it is best to avoid taking these drugs 48 hours before the TPMT enzyme activity test.

The TPMT genotyping tool detects the three most prevalent mutations associated to TPMT deficiency in a large population. This test is accurate to 96%. The TPMT testing can miss rare variants. However, it is possible to differentiate between mutant and wild-type patients by using large samples. TPMT is the preferred test for detecting TPMT mutants in large numbers, despite these limitations.

Asian populations are not well-versed in TPMT activity. Three ethnic groups were investigated for TPMT activity in Singapore. The authors employed a radiochemical assay to measure the TPMT activity in red blood cells. To validate the cutoffs for intermediate levels of TPMT activity, a receiver-operating curve analysis was conducted. The authors also used PCR to screen TPMT*3C variants.

Four common allele variants exist in the TPMT genes, namely *2 (238 G–C). These mutations occur in 0.4% of patients with thiopurine drug related cancers. TPMT variant genetic testing is helpful in optimizing 6-MP treatment. These patients should undergo TPMT genotyping to determine if they have a genetic condition.

UK gastroenterologists generally view TPMT testing with caution. The British Society of Gastroenterology recognises the importance of this test but recommends TPMT tests only for patients who are at risk of developing leukaemia. It is not intended to replace routine monitoring. TPMT testing can help determine when to intervene if a patient has severe Leucopenia.

A study was done using PCR and RFLP to determine the frequencies TPMT polymorphisms. The study involved 326 individuals who were chosen from a Southern Indian population. The results of the allele-specific oligonucleotide oligonucleotide PCR (PCR) were summarized in Tables 1 and 2.

Three pairs of primers in NP_000367.2 amplify three fragments of TPMT genes. These primers generate fluorescent single-stranded Target DNA. Mix the sample in a 25-ml multiplex mixture consisting of 1.5 U Taq polymerase and two-mM mgCl2 buffer. The fluorescent primers are also added.

The TPMT enzyme is a key player in the detoxification of thiopurine drugs. Among them are 6-mercapto-purine, 6-thioguanine, and azathioprine. Individuals with deficient or intermediate TPMT activity are at risk for life-threatening toxicity. Wildtype TPMT*1 is high in catalytic activity. Variants have decreased catalytic activitiy. The distribution of TPMT variants is different for each ethnicity. Only two studies have been published on Mexican populations.

TPMT test detects bone marrow toxicity

The TPMT (thiopurine methyltransferase) test measures red blood cell thiopurine methyltransferase(TPMT). It is possible to get falsely low results after a recent blood transfusion. A person's genetic makeup and the use thiopurine medication may increase the likelihood of developing bone cancer. Other drugs may inhibit TPMT activity, including benzoic acid inhibitors, naproxen, and thiazide diuretics. Taking any of these drugs 48-hours before the TPMT Test could lead to a falsely low TPMT Activity.

There are many methods to measure the TPMT activity of red blood cells. The results may be affected by recent blood transfusions, or RBC age depending on the laboratory. Alternatively, TPMT Genotype Testing can predict TPMT’s decreased activity. This test is a combination of single nucleotide primer extension and polymerization. It is necessary to obtain five mL of whole blood at room temperature.

A genetic variant within the TPMT gene can increase the risk of serious bone marrow toxicity. Due to single nucleotide variations in the TPMT genetic, TPMT activitiy can vary between patients. People with low TPMT activities are at greater risk of developing leukopenia. TPMT enzyme activity is inherited as a codominant trait, meaning that individuals with low levels of this gene are at increased risk for myelosupression.

The TPMT enzyme is a trimodal gene with a pronounced trimodal distribution pattern in people of Caucasian race. This study found that 89 % of Caucasians have a genotype which is homozygous or nearly identical to the wild-type TPMT enzyme allele. Only 11 % have one or more variants. One out of every 300 individuals with low TPMT enzyme activity is homozygous for two deficient alleles.

Although TPMT testing can only be done on a very small scale, the British Society of Gastroenterologists has acknowledged its role in leukopenia. If patients have leucopenia or preexisting conditions, TPMT testing should be done. A test is only useful if TPMT can be detected early in the illness.

TPMT-genotypes have high sensitivity, and specificity. TPMT genotypes cover 95% inactivating alleles. The TPMT genotypes can double check if the patient's heterozygous for a rare variant allele. One variant was responsible for 11% of TPMT-deficient individuals. Four patients with a TPMT*3C variation had low TPMT activity.

TPMT genotypes are recommended for patients with known TPMT deficiencies or who have recently received blood transfusions. These genotypes are not intended to replace clinical monitoring but can be used to identify individuals at higher risk of toxicity. A normal genotype cannot rule out rare variants. This could cause toxicity. A TPMT genotype with saliva gene activities may increase the test’s clinical utility.

A TPMT genotype can also be used to detect the TPMT gene underlying the anemia. People with TPMT mutations are more susceptible to thiopurine toxicity that those with normal genotypes. This disease affects the bone-marrow's ability of producing red, green, and/or platelet cells. The resulting anemia is characterized by pale skin, shortness of breath, and extreme fatigue.

De novo purine synthesis is prevented by the TPMT enzyme. It is not known if TPMT genotypes are sufficient to predict thiopurine tolerance. A TPMT mutation test is often used in conjunction with genetic analysis to determine if a patient is susceptible to thiopurine toxicity. It can also indicate the severity.