Analysis of thiopurine S-methyltransferase genotypes in Japanese patients with inflammatory bowel disease.

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 (TPMT1/*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.