Allele Frequency of Thiopurine Methyltransferase and Inosine Triphosphate Pyrophosphatase Gene Polymorphisms in Korean Patients with Inflammatory Bowel Diseases

Abstract

Background/aims Adverse reactions to thiopurines may be predisposed by thiopurine methyltransferase (TPMT) or inosine triphosphate pyrophosphatase (ITPA) gene mutations.

Methodology We examined the frequencies of TPMT and ITPA gene polymorphisms in 812 Korean patients with inflammatory bowel diseases using denaturing high performance liquid chromatography and direct sequencing.

Results The allele frequencies of TPMT*2, TPMT*3A, TPMT*3B, and TPMT*3C were 0, 0, 0, and 0.010 (17/1624), respectively. For the ITPA polymorphism, 173 subjects were heterozygous and 5 were homozygous for the 94C>A missense mutation (allele frequency of A, 0.113). Moreover, the 87T>C, IVS2+21A>C, and IVS2+53C>T polymorphisms were found in one patient each (1/1624), respectively. Of these, 87T>C and IVS2+53C>T were novel single nucleotide polymorphisms of the ITPA gene whose clinical significance should be further evaluated.

Conclusions Our data describe TPMT and ITPA gene mutation patterns among Koreans and provide a basis for screening studies to identify patients at high risk for myelotoxicity from thiopurine drugs.