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

Raju Murugesan, Abdul Vahab Saadi, Satyajit Patra, Rekha Rao, Jyothi Rao, Padmalatha Rai, P. M. Gopinath, Kapaettu Satyamoorthy

Research output: Contribution to journalArticle

11 Citations (Scopus)

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 defcient 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) defne the most prevalent mutant alleles associated with loss of catalytic activity reported in several populations. The present study investigated, for the frst 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-specifc polymerase chain reaction, restriction fragment length polymorphism and confrmatory 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 signifcant variations in TPMT gene polymorphisms in an indian population in relation to other human populations and may help to predict both clinical effcacy and drug toxicity of thiopurine drugs.

Original languageEnglish
Number of pages1
JournalExperimental and Therapeutic Medicine
Volume1
Issue number1
DOIs
Publication statusPublished - 01-2010

Fingerprint

thiopurine methyltransferase
Alleles
Genotype
Population
Single Nucleotide Polymorphism
Pharmaceutical Preparations
Heterocyclic Compounds
Thioguanine
Metagenomics
Azathioprine
Drug-Related Side Effects and Adverse Reactions
DNA Sequence Analysis
Sulfhydryl Compounds
Restriction Fragment Length Polymorphisms
Methylation
Leukocytes
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Medicine(all)
  • Cancer Research
  • Immunology and Microbiology (miscellaneous)

Cite this

@article{53335204cf514ab2ae8fbc814dd9af5a,
title = "Thiopurine S-methyltransferase alleles, TPMT*2, *3B, and *3C, and genotype frequencies in an indian population",
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 defcient 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) defne the most prevalent mutant alleles associated with loss of catalytic activity reported in several populations. The present study investigated, for the frst 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-specifc polymerase chain reaction, restriction fragment length polymorphism and confrmatory 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 signifcant variations in TPMT gene polymorphisms in an indian population in relation to other human populations and may help to predict both clinical effcacy and drug toxicity of thiopurine drugs.",
author = "Raju Murugesan and Saadi, {Abdul Vahab} and Satyajit Patra and Rekha Rao and Jyothi Rao and Padmalatha Rai and Gopinath, {P. M.} and Kapaettu Satyamoorthy",
year = "2010",
month = "1",
doi = "10.3892/etm_00000021",
language = "English",
volume = "1",
journal = "Experimental and Therapeutic Medicine",
issn = "1792-0981",
publisher = "Spandidos Publications",
number = "1",

}

Thiopurine S-methyltransferase alleles, TPMT*2, *3B, and *3C, and genotype frequencies in an indian population. / Murugesan, Raju; Saadi, Abdul Vahab; Patra, Satyajit; Rao, Rekha; Rao, Jyothi; Rai, Padmalatha; Gopinath, P. M.; Satyamoorthy, Kapaettu.

In: Experimental and Therapeutic Medicine, Vol. 1, No. 1, 01.2010.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Thiopurine S-methyltransferase alleles, TPMT*2, *3B, and *3C, and genotype frequencies in an indian population

AU - Murugesan, Raju

AU - Saadi, Abdul Vahab

AU - Patra, Satyajit

AU - Rao, Rekha

AU - Rao, Jyothi

AU - Rai, Padmalatha

AU - Gopinath, P. M.

AU - Satyamoorthy, Kapaettu

PY - 2010/1

Y1 - 2010/1

N2 - 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 defcient 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) defne the most prevalent mutant alleles associated with loss of catalytic activity reported in several populations. The present study investigated, for the frst 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-specifc polymerase chain reaction, restriction fragment length polymorphism and confrmatory 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 signifcant variations in TPMT gene polymorphisms in an indian population in relation to other human populations and may help to predict both clinical effcacy and drug toxicity of thiopurine drugs.

AB - 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 defcient 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) defne the most prevalent mutant alleles associated with loss of catalytic activity reported in several populations. The present study investigated, for the frst 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-specifc polymerase chain reaction, restriction fragment length polymorphism and confrmatory 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 signifcant variations in TPMT gene polymorphisms in an indian population in relation to other human populations and may help to predict both clinical effcacy and drug toxicity of thiopurine drugs.

UR - http://www.scopus.com/inward/record.url?scp=77955751800&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77955751800&partnerID=8YFLogxK

U2 - 10.3892/etm_00000021

DO - 10.3892/etm_00000021

M3 - Article

VL - 1

JO - Experimental and Therapeutic Medicine

JF - Experimental and Therapeutic Medicine

SN - 1792-0981

IS - 1

ER -