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.