BACKGROUND AND AIMS: Myelosuppression observed in patients with inflammatory bowel disease (IBD) treated with azathioprine (AZA) has been attributed to low thiopurine S-methyltransferase (TPMT) activity. TPMT activity is dependent on the genetic polymorphism of high-versus low-metabolizing alleles. We investigated the association between TPMT genotypes and myelosuppression in Japanese IBD patients. METHODS: Forty-one healthy volunteers and 70 IBD patients (UC, n = 50; CD, n = 20) were recruited. All IBD patients were treated with AZA. The TPMT genotypes were determined by polymerase-chain reaction-restriction fragment length polymorphism (PCR-RFLP) analyses. RESULTS: One healthy volunteer showed a heterozygous mutation of TPMT*1/*3C. All other volunteers and the 70 IBD patients were of the wild alleleotype (TPMT*1/*1). In the IBD patients, 7 patients developed leucopenia (<3,000/microL). One of them developed severe leucopenia (<1,000 microL) with agranulocytosis on day 14 after drug initiation. CONCLUSION: TPMT mutations are not associated with myelosuppression in Japanese IBD patients. Even in IBD patients with a wild TPMT genotype, clinicians should pay attention for the possible development of myelosuppression.
BACKGROUND AND AIMS: Myelosuppression observed in patients with inflammatory bowel disease (IBD) treated with azathioprine (AZA) has been attributed to low thiopurine S-methyltransferase (TPMT) activity. TPMT activity is dependent on the genetic polymorphism of high-versus low-metabolizing alleles. We investigated the association between TPMT genotypes and myelosuppression in Japanese IBDpatients. METHODS: Forty-one healthy volunteers and 70 IBDpatients (UC, n = 50; CD, n = 20) were recruited. All IBDpatients were treated with AZA. The TPMT genotypes were determined by polymerase-chain reaction-restriction fragment length polymorphism (PCR-RFLP) analyses. RESULTS: One healthy volunteer showed a heterozygous mutation of TPMT*1/*3C. All other volunteers and the 70 IBDpatients were of the wild alleleotype (TPMT*1/*1). In the IBDpatients, 7 patients developed leucopenia (<3,000/microL). One of them developed severe leucopenia (<1,000 microL) with agranulocytosis on day 14 after drug initiation. CONCLUSION:TPMT mutations are not associated with myelosuppression in Japanese IBDpatients. Even in IBDpatients with a wild TPMT genotype, clinicians should pay attention for the possible development of myelosuppression.
Authors: Y Kakuta; T Naito; M Onodera; M Kuroha; T Kimura; H Shiga; K Endo; K Negoro; Y Kinouchi; T Shimosegawa Journal: Pharmacogenomics J Date: 2015-06-16 Impact factor: 3.550