Research Description:

Evaluation of DNA Variation in Immunosuppressive Drug Response in Transplant Patients

Transplantation uses immunosuppresant drugs to keep the body from recognizing a transplanted organ as "foreign". There is a large degree of interpatient variability in dosing immunosuppresants, it is believed that this variability may be caused by slight differences in protein structure. Tacrolimus (FK506) is an immunosuppresant that binds to a specific protein (FK binding protein 12) and the drug-protein complex together inhibits immune response. An altered form of the FK binding protein will not bind as efficiently to tacrolimus, and the patient may have a poor response to the drug. Digression in protein structure may result from a polymorphism (PM), or a variation in the genetic code. My project involves the search for polymorphisms in the coding region for the FK binding protein through DNA isolating and computer sequencing techniques. The study design includes enrolling transplant patients and isolating their DNA from buccal cells (cheek cells). The target including the PM is amplified by PCR (polymerase chain reaction) then sequenced to allow for PM identification. In the process of searching for this PM, an extensive transplant patient DNA bank will be established that will be used for future PM searches concerning other drug targets.