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* = Presenting author

P407 Clinical manifestations of thiopurine S-methyltransferase variants in Korean paediatric patients with inflammatory bowel disease

M. Kim*

Inje University College of Medicine, Ilsan Paik Hospital, Paediatrics, Goyang-si, Gyeonggi-do, South Korea

Background

Azathioprine (AZA) is used to maintain clinical remission in inflammatory bowel disease (IBD). Thiopurine S-methyltransferase (TPMT) is the key enzyme in the metabolic pathway of thiopurine compounds, and its activity is largely influenced by polymorphisms of the TPMT gene. This study evaluated the clinical manifestations of TPMT variants in Korean paediatric IBD patients.

Methods

In total, 293 IBD patients who required AZA to maintain remission were genotyped for TPMT. There were 209 Crohn’s disease patients and 84 ulcerative colitis patients, ranging in age from 3 to 21 years. We carried out a complete sequencing analysis to screen all TPMT variants in paediatric patients and assessed the clinical manifestations including adverse drug reactions (ADR), WBC counts, and optimal AZA dose in TPMT variants.

Results

TPMT variants were detected in 12 amongst 293 patients (4.1%). TPMT*3C was found in 9 patients (3.1%); TPMT*1/*3C in 8 patients (2.7%); and TPMT*3C/*3C in 1. Rare TPMT variants including TPMT*6 and TPMT*16 were detected in 3 patients (1.0%). The patient with *3C/*3C mutation had prominent leukopenia and required a low dose of AZA, 0.18 mg/kg/day to maintain an optimal therapeutic range of 6-thioguanine nucleotide (6-TGN). Further, 3 of 8 patients with *1/*3C mutation had ADR such as leukopenia, rash, and hair loss, and 1 of 2 patients with *1/*6 mutation had nausea. However, 1 patient with *1/*16 mutation did not present any ADR.

Conclusion

TPMT*3C was the most frequent TPMT variant, and TPMT*6 was the second most common. Although TPMT genotype could not completely explain the thiopurine-induced ADR, it could be helpful to examine TPMT genotypes before administering AZA. The results of our study will be useful for future clinical studies on TPMT pharmacogenetics and dosage adjustment in the Asian IBD population.