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Title of Journal: Eur J Clin Pharmacol

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Abbravation: European Journal of Clinical Pharmacology

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Springer-Verlag

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1432-1041

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Thiopurine Smethyltransferase activity in three m

Authors: Shirley Kow Yin Kham Chin Kok Soh Te Chih Liu Yiong Huak Chan Hany Ariffin Poh Lin Tan Allen Eng Juh Yeoh
Publish Date: 2008/01/11
Volume: 64, Issue: 4, Pages: 373-379
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Abstract

The distribution of thiopurine methyltransferase TPMT activity in Asian populations has not been well documented We studied the TPMT phenotype in three major Asian ethnic groups in Singapore namely the Chinese Ch Malays Mal and Indians Ind with the aim of carrying out a comprehensive survey of the distribution of TPMT activity in AsiansA radiochemical assay was used to measure the enzymatic activity of TPMT in the red blood cells RBCs of 479 healthy adults Ch = 153 Mal = 163 and Ind = 163 Cutoff points for intermediate TPMT activity were validated using a receiver operating curve ROC analysis PCRbased methods were used to screen for the TPMT3C TPMT3A and TPMT6 variantsThe histogram of the combined population cohort showed a bimodal distribution of TPMT activity with no subject having low TPMT activity 5 units In total TPMT variants were detected in 14 subjects 1/3C in 13 subjects 1/3A in one subject We observed significant interethnic differences in terms of TPMT activity p  0001 with the Malays showing a higher median activity than the Chinese or Indians 178 units vs 164 units The Malays also showed a higher methylation rate – with a cutoff point for intermediate TPMT activity of 113 units – than the Chinese 99 units or Indians 94 units A high phenotype–genotype correlation of 97 was observed in all three races We also genotyped 418 childhood leukaemias The combined analysis of subjects participating in this and a previous study – 1585 subjects – showed that 47 of Chinese n = 30/644 44 of Malays n =  24/540 and 27 of Indians n = 11/401 were heterozygous at the TPMT gene locusWe would like to thank Dr Richard Weinshilboum and Carol Szumlanski from the Mayo Clinic College of Medicine Rochester for providing the training in TPMT phenotyping This research is funded by National Medical Research Council NMRC 0582/2001 and Children Cancer Foundation

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