Thiopurine S-methyltransferase alleles, TPMT*2, *3B and *3C, and genotype frequencies in an Indian population

  • Authors:
    • Raju Murugesan
    • Saadi A. Vahab
    • Satyajit Patra
    • Rekha Rao
    • Jyothi Rao
    • Padmalatha Rai
    • P. M. Gopinath
    • Kapaettu Satyamoorthy
  • View Affiliations

  • Published online on: January 1, 2010     https://doi.org/10.3892/etm_00000021
  • Pages: 121-127
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Abstract

Thiopurine S-methyltransferase (TPMT) catalyzes the S-methylation of aromatic and heterocyclic sulfhydryl compounds including thiopurine drugs such as 6-mercapto-purine, 6-thioguanine and azathioprine. TPMT activity exhibits genetic variation and shows tri-modal distribution with 89-94% of individuals possessing high activity, 6-11% intermediate activity and approximately 0.3% low activity. Patients with intermediate or deficient TPMT activity exposed to thiopurine drugs show severe hematopoietic toxicity. Three single nucleotide polymorphisms (SNPs) in TPMT (NM_000367.2:c.238G>C, NM_000367.2:c.460G>A and NM_000367.2:c.719A>G) define the most prevalent mutant alleles associated with loss of catalytic activity reported in several populations. The present study investigated, for the first time, the frequency distribution of these three SNPs of TPMT, their alleles and genotypes in a Southern Indian population. Peripheral blood was obtained from 326 individuals of a Southern Indian population, and genomic DNA was isolated from total peripheral white blood cells. The genotypes at the polymorphic loci were determined by allele-specific polymerase chain reaction, restriction fragment length polymorphism and confirmatory DNA sequencing. The estimated genotype frequency for homozygous TPMT*1/*1 was 97.24%, for heterozygous TPMT*1/*2 and TPMT*1/*3B, 0.61% each, and for heterozygous TPMT*1/*3C, 1.53%. The frequency of heterozygous mutants in the studied Indian population was 2.76%. This study demonstrated significant variations in TPMT gene polymorphisms in an Indian population in relation to other human populations and may help to predict both clinical efficacy and drug toxicity of thiopurine drugs.
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January-February 2010
Volume 1 Issue 1

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Murugesan R, Vahab SA, Patra S, Rao R, Rao J, Rai P, Gopinath PM and Satyamoorthy K: Thiopurine S-methyltransferase alleles, TPMT*2, *3B and *3C, and genotype frequencies in an Indian population . Exp Ther Med 1: 121-127, 2010.
APA
Murugesan, R., Vahab, S.A., Patra, S., Rao, R., Rao, J., Rai, P. ... Satyamoorthy, K. (2010). Thiopurine S-methyltransferase alleles, TPMT*2, *3B and *3C, and genotype frequencies in an Indian population . Experimental and Therapeutic Medicine, 1, 121-127. https://doi.org/10.3892/etm_00000021
MLA
Murugesan, R., Vahab, S. A., Patra, S., Rao, R., Rao, J., Rai, P., Gopinath, P. M., Satyamoorthy, K."Thiopurine S-methyltransferase alleles, TPMT*2, *3B and *3C, and genotype frequencies in an Indian population ". Experimental and Therapeutic Medicine 1.1 (2010): 121-127.
Chicago
Murugesan, R., Vahab, S. A., Patra, S., Rao, R., Rao, J., Rai, P., Gopinath, P. M., Satyamoorthy, K."Thiopurine S-methyltransferase alleles, TPMT*2, *3B and *3C, and genotype frequencies in an Indian population ". Experimental and Therapeutic Medicine 1, no. 1 (2010): 121-127. https://doi.org/10.3892/etm_00000021