Thiopurine methyltransferase enzyme activity
Thiopurine methyltransferase (TPMT) is a protein present in the organism to metabolize thiopurines, substances that play an important role in the regulation of the immunologic system and in the treatment of diverse diseases of the blood, autoimmune system or some cancers. The thiopurines include azathioprine (AZA) and its derivative 6-mercaptopurine which is administered as medication to combat these conditions, and thiopurine methyltransferase (TPMT) is the principal metabolizing enzyme.
The presence of TPMT in the organism, both in its levels and in its adequate functionality, is regulated by specific genes that are implicated in its correct synthesis. There are different mutations in the genes resulting in a TPMT deficiency. This disorder is generally autosomal recessive inherited, i.e., both parents are asymptomatic carriers of said mutation and who pass the mutated gene to their children. These, in turn, inherit the TPMT deficiency.
Azathioprine is an immunosuppressive drug derived from mercaptopurine that is a metabolic antagonist of purines. It is preferentially used for autoimmune diseases with insufficient response to corticoids as well as in preventing rejection of organ transplants in patients (associated with other immunosuppressants). The most important secondary effects of azathioprine are medullary depression, gastrointestinal intolerance and hepatotoxicity. It should be used carefully in patients who have gout or bacterial infections. Hematologic and biochemical controls should be done periodically.
When there is a malfunction that affects said genes, it can lead to a TPMT deficiency, and with it an abnormal metabolism of thiopurines. In most people this deficiency does not incur any health problems since treatment with azathioprine or 6-mercaptopurine is not frequent. Nevertheless, those who do receive said medicines and have a TPMT deficiency, metabolize these medications more slowly and may experience more irregular responses and a greater amount of adverse effects. Some of those include nausea and a transaminase increase, besides others that are more serious such as medullary suppression (inability to make new blood cells).
Gene or region studied