The impact of thiopurine S-methyltransferase polymorphisms on azathioprine dose 1 year after renal transplantation.
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 genot...
| Main Authors: | , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2004
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| _version_ | 1797103197871931392 |
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| author | Fabre, M Jones, D Bunce, M Morris, P Friend, P Welsh, K Marshall, SE |
| author_facet | Fabre, M Jones, D Bunce, M Morris, P Friend, P Welsh, K Marshall, SE |
| author_sort | Fabre, M |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T06:16:38Z |
| format | Journal article |
| id | oxford-uuid:f14b3732-6fbc-4db4-b767-8f78b0464858 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:16:38Z |
| publishDate | 2004 |
| record_format | dspace |
| spelling | oxford-uuid:f14b3732-6fbc-4db4-b767-8f78b04648582022-03-27T11:54:57ZThe impact of thiopurine S-methyltransferase polymorphisms on azathioprine dose 1 year after renal transplantation.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f14b3732-6fbc-4db4-b767-8f78b0464858EnglishSymplectic Elements at Oxford2004Fabre, MJones, DBunce, MMorris, PFriend, PWelsh, KMarshall, SEAzathioprine 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. |
| spellingShingle | Fabre, M Jones, D Bunce, M Morris, P Friend, P Welsh, K Marshall, SE The impact of thiopurine S-methyltransferase polymorphisms on azathioprine dose 1 year after renal transplantation. |
| title | The impact of thiopurine S-methyltransferase polymorphisms on azathioprine dose 1 year after renal transplantation. |
| title_full | The impact of thiopurine S-methyltransferase polymorphisms on azathioprine dose 1 year after renal transplantation. |
| title_fullStr | The impact of thiopurine S-methyltransferase polymorphisms on azathioprine dose 1 year after renal transplantation. |
| title_full_unstemmed | The impact of thiopurine S-methyltransferase polymorphisms on azathioprine dose 1 year after renal transplantation. |
| title_short | The impact of thiopurine S-methyltransferase polymorphisms on azathioprine dose 1 year after renal transplantation. |
| title_sort | impact of thiopurine s methyltransferase polymorphisms on azathioprine dose 1 year after renal transplantation |
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