Document Detail

Thiopurine S-methyltransferase alleles, TPMT(*)2, (*)3B and (*)3C, and genotype frequencies in an Indian population.
MedLine Citation:
PMID:  23136604     Owner:  NLM     Status:  Publisher    
Thiopurine S-methyltransferase (TPMT) catalyzes the S-methylation of aromatic and heterocyclic sulfhydryl compounds including thiopurine drugs such as 6-mercaptopurine, 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.
Raju Murugesan; Saadi Abdul Vahab; Satyajit Patra; Rekha Rao; Jyothi Rao; Padmalatha Rai; P M Gopinath; Kapaettu Satyamoorthy
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2010-1-1
Journal Detail:
Title:  Experimental and therapeutic medicine     Volume:  1     ISSN:  1792-1015     ISO Abbreviation:  Exp Ther Med     Publication Date:  2010 1 
Date Detail:
Created Date:  2012-11-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101531947     Medline TA:  Exp Ther Med     Country:  -    
Other Details:
Languages:  ENG     Pagination:  121-127     Citation Subset:  -    
Manipal Life Sciences Center, Manipal University, Manipal 576104, India.
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