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


CONCLUSIONS
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.
Ban
Hiromitsu
H
Department of Medicine, Shiga University of Medical Science, Otsu.
Andoh
Akira
A
Tanaka
Aiko
A
Tsujikawa
Tomoyuki
T
Sasaki
Masaya
M
Saito
Yasuharu
Y
Fujiyama
Yoshihide
Y
D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D001379:Azathioprine / Q000009:adverse effects / Q000627:therapeutic use; D001853:Bone Marrow / Q000187:drug effects; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D003424:Crohn Disease / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics*; D007564:Japan; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008780:Methyltransferases / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation; D055815:Young Adult
D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine