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.
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.
Authors: Ana Teresa P Carvalho; Barbara C Esberard; Renata S B Fróes; Davy C M Rapozo; Ana B Grinman; Tatiana A Simão; Juliana C V C Santos; Antonio José V Carneiro; Luis Felipe Ribeiro-Pinto; Heitor S P de Souza Journal: World J Gastroenterol Date: 2014-03-28 Impact factor: 5.742
Authors: N Chantal Peltenburg; Jörgen Bierau; Jaap A Bakker; Jolanda A Schippers; Selwyn H Lowe; Aimée D C Paulussen; Bianca J C van den Bosch; Mathie P G Leers; Bettina E Hansen; Annelies Verbon Journal: PLoS One Date: 2018-01-12 Impact factor: 3.240
Authors: Hyery Kim; Heewon Seo; Yoomi Park; Byung-Joo Min; Myung-Eui Seo; Kyung Duk Park; Hee Young Shin; Ju Han Kim; Hyoung Jin Kang Journal: Cancer Res Treat Date: 2017-09-04 Impact factor: 4.679