The impact of thiopurine S-methyltransferase polymorphisms on azathioprine dose 1 year after renal transplantation.
Transpl Int
; 17(9): 531-9, 2004 Oct.
Article
em En
| MEDLINE
| ID: mdl-15349717
ABSTRACT
Azathioprine metabolism is influenced by activity of the enzyme thiopurine S-methyltransferase (TPMT), which varies markedly between individuals. In this study we examined the influence of TPMT gene polymorphisms on azathioprine dose 1 year after renal transplantation. TPMT coding and promoter genotypes were determined using PCR-based assays. Azathioprine dose, white cell count, and intercurrent events throughout the first year after renal transplantation were ascertained from contemporaneous clinical notes. All patients analysed ( n=172) received an initial azathioprine dose of 1.5 mg/kg per day. Twelve individuals with one variant TPMT coding allele were detected (*3A n=11, *3C n=1). Of these, 58% required azathioprine dose reduction because of leucopenia, compared to only 30% of homozygous wild-type patients ( P=0.04). A significant correlation between the presence of >/=11 variable number tandem repeats (VNTRs) in the TPMT promoter and reduction in azathioprine dose was also identified ( P=0.001). We concluded that when azathioprine is administered at an initial dose of 1.5 mg/kg per day, both coding and promoter TPMT polymorphisms influence the dose tolerated.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polimorfismo Genético
/
Azatioprina
/
Transplante de Rim
/
Imunossupressores
/
Metiltransferases
Tipo de estudo:
Observational_studies
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Transpl Int
Assunto da revista:
TRANSPLANTE
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Reino Unido