TPMT genotype and its clinical implication in renal transplant recipients with azathioprine treatment.
BACKGROUND
Thiopurine S-methyltransferase (TPMT) catalyses the S-methylation of thiopurine drugs. Patients with intermediate or deficient TPMT activity are at risk of toxicity after receiving standard doses of these drugs.


OBJECTIVE
This study determined the frequencies of TPMT alleles (TPMT*2, *3A, *3B and *3C) and explored the association between TPMT genetic polymorphism and the development of adverse drug reactions in Chinese renal transplant patients receiving azathioprine (AZA).


METHODS
TPMT genotypes were determined using polymerase chain reaction-based assays in 122 renal transplant patients and 210 healthy subjects. Biochemical and clinical data were retrospectively evaluated after renal transplantation.


RESULTS
Of 122 patients, eight (allele frequency 3.28%) were heterozygous for TPMT*3C and no TPMT*2, *3A or *3B or homozygous TPMT*3C subjects were identified. The pattern and frequency of the main mutant TPMT alleles were similar in patients and healthy subjects. Four of five patients (80%) with haematopoietic toxicity were heterozygotes. TPMT heterozygosity was associated with significant reductions in haematological indices and a significant decrease in cyclosporine plasma concentrations in the first year after renal transplantation. No association between TPMT genotype and renal rejection was identified.


CONCLUSIONS
Our results, together with those of others pointing in the same direction, suggest that genotyping the major TPMT variant alleles may be a valuable tool in preventing AZA toxicity and optimization of immunosuppressive therapy.
Song
D-K
DK
Department of Urology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, China.
Zhao
J
J
Zhang
L-R
LR
D000293:Adolescent; D000328:Adult; D000368:Aged; D001379:Azathioprine / Q000009:adverse effects*; D016572:Cyclosporine / Q000097:blood; D005260:Female; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D016030:Kidney Transplantation; D008297:Male; D008780:Methyltransferases / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine