Identification of single nucleotide polymorphisms in inflammatory bowel disease patients on azathioprine therapy

Abstract

Azathioprine, an immunosuppressant used for many years in the medical sector to maintain long term disease remission in inflammatory bowel disease has a side effect profile that has raised many concerns over the years with numerous studies into the risk, cause and prevention of these adverse events. It is estimated that 18 in every 100 000 South Africans suffer from Crohn's disease, while 5 in every 100 000 suffer from ulcerative colitis. Of these inflammatory bowel disease patients at least 20% will suffer from leukopenia and eventually bone marrow suppression. Much of the side effect profile of Azathioprine can be linked to a single nucleotide polymorphism in the thiopurine methyltransferase gene which ensures the breakdown and efficacy of Azathioprine. The thiopurine methyltransferase single nucleotide polymorphism profiles of various American, Asian and European populations have been studied, but little literature is available for the South African population. The aim of this study was to determine if it is essential to include "early warning" single nucleotide polymorphism testing in South African health care before treatment with Azathioprine is initiated. This was performed by evaluating 40 patients suffering from inflammatory bowel disease who met the inclusion/ exclusion criteria and who were on continuous Azathioprine therapy. The prevalence of *3A, *3B or *3C thiopurine methyltransferase gene SNP’s were determined to assess the efficacy of Azathioprine in reducing therapeutic markers and to compare the frequency of SNP’s within the Azathioprine dosing groups. This study showed an increase in the allelic frequency of thiopurine methyltransferase *3B and a statistically significant presence (p<0.001) of homozygous thiopurine methyltransferase *3B alleles in South African inflammatory bowel disease patients when compared to healthy South African individuals- this has not previously been reported in published literature. Thus, in future, the enzymatic effect of thiopurine methyltransferase *3B/*3B should be studied in a larger sample size prior to recommending early warning single nucleotide polymorphism testing in inflammatory bowel disease patient using Azathioprine as these results cannot be ignored.