Testing recommended prior to initiation of thiopurine
therapy. Thiopurine drug therapy is used for autoimmune diseases,
inflammatory bowel disease, acute lymphoblastic leukemia, and to prevent
rejection after solid organ transplant. Thiopurine methyltransferase
(TPMT) is an enzyme that
breaks down (metabolises) a class of drugs called thiopurines.Examples of
thiopurines include azathioprine, mercaptopurine, and thioguanine. These drugs
are used to suppress the immune system and
are prescribed to treat various immune-related conditions or blood disorders
(e.g., leukaemia).
The activity level of the TPMT enzyme, or the genetics underlying the enzyme's
activity, is tested before thiopurine drug therapy to make sure that
individuals treated with the drugs can metabolise them.
TPMT genetic test (genotype)
is a genetic test that can identify genetic variations in the TPMT gene. Three
milliliter EDTA blood sample can be collected and sent to laboratory for
testing purpose. Genomic DNA from patient sample isolated and used for
Polymerase chain reaction including gene responsible for Thiopurine
methyltransferase. Single nucleotide polymorphism (SNP) analyzed by sequence
data received by DNA sequencing technology.
About one person in every 300 is
severely deficient in TPMT, and about 10 per cent of the population has lower
than normal levels of TPMT. The side effects can be avoided if TPMT production
is tested before starting thiopurine treatment.
This genetic test provides
information about a person's likely response to thiopurines, but it will not
quantify how much TPMT enzyme is actually being made by the body. There can be
significant person-to-person and ethnic variability in TPMT production, even in
people with the same gene variations.
Gene (Transcript) Allele TPMT (NM_000367) TPMT*2 : rs1800462, c.238G>C TPMT*3A : rs1800460, c.460G>A; rs1142345, c.719A>G TPMT*3B : rs1800460, c.460G>A TPMT*3C : rs1142345, c.719A>G.
This test was developed and its performance characteristics determined by geneOmbio Technologies Pvt Ltd.
There are ways to determine
whether an individual is at risk of side effects from thiopurine therapy:
This test identifies individual
genetic differences associated with risk for thiopurine toxicity. Each person
has two copies of the TPMT gene. Most people have two copies of
"wild type" TPMT that produce sufficient TPMT enzyme.
Approximately 10 per cent of people have one wild-type gene and one gene variation
associated with decreased TPMT (heterozygous)
and intermediate enzyme activity.
While numerous variations (SNP) can occur in TPMT, above mentioned five
variations in particular that have been proven to be associated with TPMT
deficiencies.