Thiopurine S-methyltransferase (TPMT) pharmacogenetics: three new mutations and haplotype analysis in the Estonian population.
Clin Chem Lab Med
; 46(7): 974-9, 2008.
Article
in En
| MEDLINE
| ID: mdl-18605963
ABSTRACT
BACKGROUND:
Thiopurine methyltransferase (TPMT) is a cytoplasmic enzyme involved in the metabolism of thiopurine drugs. To date, at least 25 single nucleotide polymorphisms have been reported in the TPMT gene, 23 of these are associated with reduced enzyme activity.METHODS:
The aim of the present study was to sequence the whole coding region of TPMT (exons 3-10) to identify known and novel TPMT sequence variants amongst healthy Estonians. Erythrocyte TPMT activity was also measured to carry out a genotype-phenotype comparison.RESULTS:
A total of 21 subjects were heterozygous for known TPMT alleles (*2, *3A, *3C, *9, *12). Several other previously described intronic and exon polymorphisms were identified. Three novel mutations were detected -30T>A in exon 3, 10A>G in intron 3, and 145A>G in intron 10. Association analysis revealed four markers (114T>A, 94T>A, 460G>A, 719A>G) whose frequencies were significantly different in intermediate (enzyme activityCONCLUSIONS:
Our results point to several markers that predict reduced enzyme activity. None of the identified markers were associated with high enzyme activity.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Haplotypes
/
Methyltransferases
/
Mutation
Type of study:
Prognostic_studies
Limits:
Adolescent
/
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Country/Region as subject:
Europa
Language:
En
Journal:
Clin Chem Lab Med
Journal subject:
QUIMICA CLINICA
/
TECNICAS E PROCEDIMENTOS DE LABORATORIO
Year:
2008
Document type:
Article
Affiliation country:
Estonia