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Thiopurine Drugs (thiopurine + drug)
Selected AbstractsMolecular analysis of the thiopurine S-methyltransferase alleles in Bolivians and TibetansJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 5 2005H.-F. Lu MT Summary Background:, Thiopurine drugs are used as immunosuppressant or cytotoxic drugs. Thiopurine S-methyltransferase (TPMT) methylates and thereby modulates the therapeutic and toxic effects of these drugs. The activity of TPMT is affected by genetic polymorphism of TPMT alleles, and these alleles have not been studied in Tibetans and Bolivians. Objectives:, To analyse the TPMT allelic frequencies in Tibetans and Bolivians. Methods:, We developed an inexpensive method for collecting blood and extracting genomic DNA. Genomic DNA was extracted from blood spots of 50 Tibetans and 115 Bolivians. The frequencies of allelic variants of TPMT gene (TPMT*1 to TPMT*8) were determined using polymerase chain reaction-restriction fragment length polymorphism technique. Results:, The allelic frequencies of TPMT*1 were 99 and 93ˇ48% for Tibetans and Bolivians, respectively. The corresponding allelic frequencies of TPMT*3A were 0 and 6ˇ52% and those of TPMT*3C were 1ˇ0 and 0%. No TPMT*2, 3B, 3D, 4,8 were found in these two populations. Conclusions:, As with Caucasian populations, TPMT*3A is the most prevalent mutant allele in Bolivians. Our results may be of value in helping to guide the prescription of thiopurine drugs in these populations. [source] Thiopurine S -methyltransferase (TPMT) genetic polymorphisms in Mexican newbornsJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 6 2009A. González-del Angel MD Abstract Background:, Thiopurine S -methyltransferase (TPMT) is involved in the toxicity and therapeutic efficacy of thiopurine drugs, and its gene exhibits genetic polymorphisms that differ across diverse populations. Four TPMT polymorphisms (TPMT*2, *3A, *3B and *3C) account for 80,95% of alleles that cause reduced enzyme activity. To date, only a single study in the Mexican population involving 108 individuals has been performed, but the regional and ethnic origin of this population was not described. Accordingly, information about the TPMT polymorphism in the Mexican population is limited. Objective:, To determine the TPMT allele and genotype frequencies in a sample of newborns from Mexico City. Methods:, Three hundred and sixty DNA samples from unrelated, anonymous individuals were obtained from dried blood spots collected on filter paper as part of the Newborn Screening National Program. Allele-specific polymerase chain reaction for the TPMT*2 allele and PCR restriction fragment length polymorphism for TPMT*3A, TPMT*3B, TPMT*3C alleles were used to determine the respective allelic and genotypic frequencies. Results and Discussion:, Of 720 TPMT alleles analysed, 49 (6ˇ81%) were deficiency alleles. The most common deficiency allele was TPMT*3A (5ˇ69%), followed by TPMT*3C (0ˇ56%), TPMT*3B (0ˇ28%) and TPMT*2 (0ˇ28%). Fourty-five newborns were heterozygous for one mutant allele (12ˇ5%) and two showed a genotype with two deficiency alleles (0ˇ56%). Despite its unique ethnic composition, our Mexican population exhibited variant allele frequencies that were similar to some Caucasian populations. Conclusion:, Our data suggest that approximately 1 in 180 persons born in Mexico City might have low or undetectable TPMT enzyme activity, a frequency that, overall, is somewhat higher than that reported for Caucasian populations generally (1 in 300). [source] Molecular analysis of thiopurine S -methyltransferase alleles in Taiwan aborigines and TaiwaneseJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 1 2006H-F. Lu MS Summary Background:, Thiopurine S -methyltransferase (TPMT) is a cytosolic enzyme involved in the metabolism of these thiopurine drugs. Methylation of thiopurine drugs by TPMT competes with the formation of their active 6-thioguanine nucleotide metabolite, thereby potentially modulating the therapeutic and toxic effects of these drugs. Objective:, To analyze the thiopurine S -methyltransferase allelic frequencies in Taiwan aborigines and Taiwanese. Methods:, We used polymerase chain reaction,restriction fragment length polymorphism method to determine the allelic frequencies of TPMT variants (TPMT*1,TPMT*8) in 409 Taiwan aborigines and 117 Taiwanese. Results and discussion:, The results showed that the allelic frequencies of TPMT*1 were 99ˇ88% and 98ˇ72% for Taiwan aborigines and Taiwanese respectively. The allelic frequencies of TPMT*3C were 0ˇ12% and 1ˇ28% for Taiwan aborigines and Taiwanese respectively. No TPMT*2, 3A, 3B, 3D and 4,8 were found in these populations. Conclusion:, Our results provide useful information for using thiopurine drugs in these populations. [source] Molecular analysis of the thiopurine S-methyltransferase alleles in Bolivians and TibetansJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 5 2005H.-F. Lu MT Summary Background:, Thiopurine drugs are used as immunosuppressant or cytotoxic drugs. Thiopurine S-methyltransferase (TPMT) methylates and thereby modulates the therapeutic and toxic effects of these drugs. The activity of TPMT is affected by genetic polymorphism of TPMT alleles, and these alleles have not been studied in Tibetans and Bolivians. Objectives:, To analyse the TPMT allelic frequencies in Tibetans and Bolivians. Methods:, We developed an inexpensive method for collecting blood and extracting genomic DNA. Genomic DNA was extracted from blood spots of 50 Tibetans and 115 Bolivians. The frequencies of allelic variants of TPMT gene (TPMT*1 to TPMT*8) were determined using polymerase chain reaction-restriction fragment length polymorphism technique. Results:, The allelic frequencies of TPMT*1 were 99 and 93ˇ48% for Tibetans and Bolivians, respectively. The corresponding allelic frequencies of TPMT*3A were 0 and 6ˇ52% and those of TPMT*3C were 1ˇ0 and 0%. No TPMT*2, 3B, 3D, 4,8 were found in these two populations. Conclusions:, As with Caucasian populations, TPMT*3A is the most prevalent mutant allele in Bolivians. Our results may be of value in helping to guide the prescription of thiopurine drugs in these populations. [source] Exposure to thiopurine drugs through breast milk is low based on metabolite concentrations in mother-infant pairsBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 4 2006Sharon J. Gardiner Aims To determine infant exposure to 6-thioguanine and 6-methylmercaptopurine nucleotides (6-TGN and 6-MMPN, respectively) during maternal use of azathioprine in breastfeeding. Methods Mother-infant pairs provided blood for determination of 6-TGN and 6-MMPN concentrations, and TPMT genotype. Results Four women taking azathioprine 1.2,2.1 mg kg,1 day,1 and their infants were studied. All had the wild-type TPMT genotype. Maternal 6-TGN and 6-MMPN concentrations ranged from 234 to 291 and 284 to 1178 pmol per 8 × 108 red blood cells, respectively, and were consistent with those associated with improved therapeutic outcomes. Neither 6-TGN nor 6-MMPN was detected in any of the infants, despite a sensitive assay. Conclusions The data suggest that azathioprine may be ,safe' during breastfeeding in patients with the wild-type TPMT genotype (,90% of caucasian patients) taking ,normal' doses. [source] | ||||||||||