Original articleInosine Triphosphate Pyrophosphatase and Thiopurine S-Methyltransferase Genotypes Relationship to Azathioprine-Induced Myelosuppression
Section snippets
Patient Selection
A retrospective cross-sectional study was performed by the Department of Gastroenterology and Hepatology of the Academic Medical Center, Amsterdam, the Netherlands. Medical records of all consecutive IBD patients who visited the IBD outpatient clinic from October 1995 until September 2003 were reviewed. Patients with a positive history of AZA use for whom reliable data on AZA use and related side effects could be obtained were eligible for the study. The indication and regimen of AZA treatment
Patients
A total of 262 IBD patients were included in this study. The mean AZA dose received in the whole patient population was 132 mg (range, 50–250 mg), with a mean duration of AZA exposure of 35 months (range, 1–143 mo). Patient characteristics are shown in Table 1.
Gene encoding inosine triphosphate pyrophosphatase and thiopurine S-methyltransferase allele frequencies
Allelic variants of ITPA and TPMT genes and their frequencies are shown in Table 2. Homozygosity for the ITPA 94C>A and IVS2+21A>C alleles has been found in 1 and 4 patients, respectively. Five patients were compound heterozygotes for
Discussion
We studied the allelic frequencies of earlier reported and clinically important polymorphisms of TPMT and ITPA, and their association with toxicity in IBD patients treated with AZA maintenance therapy. In this large cohort studied, we found that patients carrying TPMT (238G>C, 460G>A, and 719A>G) and ITPA (94C>A) allele mutations are at increased risk for developing leukopenia (TPMT odds ratio, 6.316; 95% CI, 2.141–18.634; P = .004; ITPA 94C>A odds ratio, 3.504; 95% CI, 1.119–10.971; P = .046).
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Z.Z. and L.J.J.D. contributed equally to this article.