title: Thiopurine S-methyltransferase activity in three major Asian populations: a population-based study in Singapore.
abstract: OBJECTIVE
  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 Asians.
  
  
  METHODS
  A 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). Cut-off points for intermediate TPMT activity were validated using a receiver operating curve (ROC) analysis. PCR-based methods were used to screen for the TPMT*3C, TPMT*3A and TPMT*6 variants.
  
  
  RESULTS
  The 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 inter-ethnic differences in terms of TPMT activity (p<0.001), with the Malays showing a higher median activity than the Chinese or Indians (17.8 units vs 16.4 units). The Malays also showed a higher methylation rate--with a cut-off point for intermediate TPMT activity of 11.3 units--than the Chinese (9.9 units) or Indians (9.4 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 4.7% of Chinese (n=30/644), 4.4% of Malays (n=24/540) and 2.7% of Indians (n=11/401) were heterozygous at the TPMT gene locus.
  
  
  CONCLUSIONS
  This is the first comprehensive TPMT phenotype and genotype study in Asian populations, particularly in the Malays and Indians.
authors.affiliation: Department of Paediatrics, National University of Singapore, and Department of Haematology-Oncology, National University Hospital, Singapore City, Republic of Singapore.
authors.forename: Shirley Kow Yin
authors.initials: SK
authors.lastname: Kham
authors.forename: Chin Kok
authors.initials: CK
authors.lastname: Soh
authors.forename: Te Chih
authors.initials: TC
authors.lastname: Liu
authors.forename: Yiong Huak
authors.initials: YH
authors.lastname: Chan
authors.forename: Hany
authors.initials: H
authors.lastname: Ariffin
authors.forename: Poh Lin
authors.initials: PL
authors.lastname: Tan
authors.forename: Allen Eng Juh
authors.initials: AE
authors.lastname: Yeoh
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005006:Ethnicity; D005260:Female; D005838:Genotype; D006801:Humans; D007194:India / Q000453:epidemiology / Q000208:ethnology; D007223:Infant; D007938:Leukemia / Q000201:enzymology / Q000235:genetics; D008297:Male; D008780:Methyltransferases / Q000378:metabolism*; D008875:Middle Aged; D010641:Phenotype; D012372:ROC Curve; D015203:Reproducibility of Results; D012846:Singapore / Q000453:epidemiology
chemical_list: D008780:Methyltransferases; C022745:thiopurine methyltransferase