Allele frequency of thiopurine methyltransferase and inosine triphosphate pyrophosphatase gene polymorphisms in Korean patients with inflammatory bowel diseases.
OBJECTIVE
Adverse reactions to thiopurines may be predisposed by thiopurine methyltransferase (TPMT) or inosine triphosphate pyrophosphatase (ITPA) gene mutations.


METHODS
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.
Cheon
Jae Hee
JH
Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.
Kim
Jae Hak
JH
Kim
Bo Young
BY
Kim
Seung Won
SW
Hong
Sung Yi
SY
Eun
Chang Soo
CS
Hong
Seong Soo
SS
Byeon
Jeong-Sik
JS
Kim
Tae Il
TI
Han
Dong Soo
DS
Yang
Suk-Kyun
SK
Lee
Kyoung Ryul
KR
Kim
Won Ho
WH
D000483:Alleles; D044466:Asian People / Q000235:genetics; D001379:Azathioprine / Q000009:adverse effects; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics*; D008297:Male; D015122:Mercaptopurine / Q000009:adverse effects; D008780:Methyltransferases / Q000235:genetics*; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011755:Pyrophosphatases / Q000235:genetics*; D000097630:Inosine Triphosphatase
D001379:Azathioprine; D007166:Immunosuppressive Agents; D015122:Mercaptopurine; D008780:Methyltransferases; D011755:Pyrophosphatases; D000097630:Inosine Triphosphatase; C022745:thiopurine methyltransferase