Molecular analysis of thiopurine S-methyltransferase alleles in South-east Asian populations

Abstract

Thiopurine S-methyltransferase (TPMT) catalyses the S-methylation of thiopurine drugs. In Caucasians, four variant TPMT alleles have been detected in over 80% of individuals with low or intermediate TPMT activity. The wild-type allele is designated as TPMT*1 and the mutant alleles are designated TPMT*2 through TPMT*8. The frequency of these alleles in different ethnic groups has not been well defined. In this study, one hundred individuals, from each of the Indonesian, Thai and Philippine populations, together with 249 Taiwanese, were analysed by polymerase chain reaction-restriction fragment length polymorphism and direct sequencing methods. The results showed that the allelic frequencies of TPMT*3C were 0.6% for Taiwanese and 1% for Filipino, Thai and Indonesian populations, respectively. One Filipino with a Caucasian parent was found to be heterozygous for the TPMT*2 allele. This study provides the first analysis of the allele frequency distribution of all known TPMT mutations in South-east Asian populations.

Thiopurine methyltransferase polymorphisms in a Brazilian population

“…10 In addition, it has been shown a trimodal allelic distribution in Caucasians, although Asians and Koreans have a unimodal distribution. 6,10,24,29,33 However, it must be noted that when determining the presence of polymorphisms in a population, ethnic and racial mixture must be taken into consideration. Thus, it is of the greatest importance to establish the genetic basis for the TPMT polymorphism in various populations, including Brazilians.…”

“…The WT allele TPMT*1 was the most prevalent, in agreement with several previous reports. 4,6,[22][23][24][25]29,33 Interestingly, in our sample the TPMT*2 (G238C) accounts for a significant number of mutant alleles. This mutation has been found only in Caucasians and is thought to represent a more recent allele.…”

“…36 The TPMT*3C allele (A719G), with a frequency of 1.0%, has been previously shown in several other ethnic groups including the Saamis, Kenyans, Ghanaians, AfricanAmerican and Asians. [22][23][24]29,30 Finally, the very uncommon allele TPMT*3B (G460A) was found in only one subject, thus indicating this allele to be a rare one. 11,16,23 To date, of the two strategies used to identify TPMT-deficient and heterozygous patients, TPMT genotype can easily be performed.…”

“…20 Furthermore, bimodal or trimodal activity patterns have been shown in several populations. 16,[21][22][23][24][25][26][27][28][29][30][31][32][33][34] Since ethnic differences have been demonstrated worldwide, it remains to be elucidated in Brazil, the fifth largest populated country in the world. The present-day Brazilian populations reflects the result of five centuries of interethnic crosses between peoples from almost all continents (Europeans, African, Asians) as well as autochthonous Amerindians, all forming one of the most heterogeneous populations in the world.…”

NUDT15 c.415C>T increases risk of 6-mercaptopurine induced myelosuppression during maintenance therapy in children with acute lymphoblastic leukemia

“…However, the frequencies of TPMT variants associated with thiopurineinduced myelosuppression in most Asian populations, including Thai, are low [7][8][9] . Determination of TPMT polymorphisms, therefore, has limited clinical benefits to children with ALL in most Asian countries.…”