Pyrosequencing of TPMT Alleles in a General Swedish Population and in Patients with Inflammatory Bowel Disease

Haglund, Sofie; Lindqvist, M.; Almér, Sven; Peterson, Curt; Taipalensuu, Jan

doi:10.1373/clinchem.2003.023846

Cited by 59 publications

(34 citation statements)

References 41 publications

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“…TPMT*3C seemed to be a unique variant allele in this Han Chinese population. The variant allele frequency was 1.47%, similar to the distribution reported in the Japanese population [26], but lower than that in Caucasians [15, 27, 28]. …”

Section: Discussionsupporting

confidence: 82%

Thiopurine Methyltransferase Gene Polymorphisms in Chinese Patients with Inflammatory Bowel Disease

Cao

Zhu²,

Shang³

et al. 2009

Digestion

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Background: The thiopurine drugs azathioprine and 6-mercaptopurine are well established in the treatment of inflammatory bowel disease (IBD). However, great interpatient variability exists in the efficacy and toxicity of the drugs, and this results from thiopurine methyltransferase (TPMT) gene polymorphisms. The aim of this study was to identify the TPMT gene polymorphisms in Chinese IBD patients and to study the relationship between TPMT status and thiopurine-related toxicity in these patients. Materials and Methods: A total of 189 IBD patients, 87 with Crohn’s disease and 102 with ulcerative colitis, and 273 healthy controls were enrolled. All subjects were from the Han Chinese ethnic group. Polymorphisms in TPMT*2, *3A, *3B and *3C were analyzed using allele-specific polymerase chain reaction and polymerase chain reaction-restriction fragment length polymorphism. Direct sequencing was used to confirm the mutation results. Exons of the TPMT gene from patients who suffered from azathioprine-induced toxicity were amplified and sequenced to detect TPMT mutations. Results: No TPMT*2, *3A or *3B mutant alleles were detected. The allele frequency of TPMT*3C in the IBD group was 1.59%, which was similar to that of the healthy control group (1.59 vs. 1.47%, p = 1.000). Forty-three patients were treated with azathioprine therapy, 4 experienced myelotoxicity, and 1 experienced hepatotoxicity, so the incidence of drug toxicity was 11.7% (5/43). No TPMT*2, *3A, *3B or *3C polymorphisms were detected in these 5 patients. After directly sequencing the exons of the TPMT gene in these 5 patients, a synonymous single-nucleotide polymorphism (TPMT*1S), which does not alter the encoded amino acid, was found in 3 patients. Conclusion: TPMT*3C seemed to be a unique variant allele in this Han Chinese population. The overall frequencies of variant TPMT alleles in this population were lower than those in Caucasians, but thiopurinetoxicity in Han Chinese IBD patients is not low. Factors other than TPMT polymorphisms may be responsible for the development of toxicity.

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Section: Discussionsupporting

confidence: 82%

Thiopurine Methyltransferase Gene Polymorphisms in Chinese Patients with Inflammatory Bowel Disease

Cao

Zhu²,

Shang³

et al. 2009

Digestion

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“…Using these cut-off levels for TPMT activity, we previously found a close relationship between TPMT genotype and phenotype. 30 …”

Section: Methodsmentioning

confidence: 99%

Mercaptopurine treatment should be considered in azathioprine intolerant patients with inflammatory bowel disease

Hindorf

Johansson

Eriksson

et al. 2009

Aliment Pharmacol Ther

101

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“…TPMT genotyping using conventional approaches has been demonstrated by a number of techniques. [37][38][39][40] Polymerase chain reaction (PCR)-based methods initially designed to genotype a small number of samples 36 are more suitable for clinical diagnostics than high-throughput detection methods developed for discovery, screening, or validation of candidate SNPs.…”

mentioning

confidence: 99%

Microfluidic Platform for Single Nucleotide Polymorphism Genotyping of the Thiopurine S-Methyltransferase Gene to Evaluate Risk for Adverse Drug Events

Chowdhury¹,

Kagiala

Pushpakom

et al. 2007

The Journal of Molecular Diagnostics

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Prospective clinical pharmacogenetic testing of the thiopurine S-methyltransferase gene remains to be realized despite the large body of evidence demonstrating clinical benefit for the patient and cost effectiveness for health care systems. We describe an entirely microchipbased method to genotype for common single nucleotide polymorphisms in the thiopurine S-methyltransferase gene that lead to serious adverse drug reactions for patients undergoing thiopurine therapy. Restriction fragment length polymorphism and allele-specific polymerase chain reaction have been adapted to a microfluidic chip-based polymerase chain reaction and capillary electrophoresis platform to genotype the common *2, *3A, and *3C functional alleles. In total, 80 patients being treated with thiopurines were genotyped, with 100% concordance between microchip and conventional methods. This is the first report of single nucleotide polymorphism detection using portable instrumentation and represents a significant step toward miniaturized for personalized treatment and automated point-of-care testing. (J Mol Diagn 2007, 9:521-529;

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Pyrosequencing of TPMT Alleles in a General Swedish Population and in Patients with Inflammatory Bowel Disease

Cited by 59 publications

References 41 publications

Thiopurine Methyltransferase Gene Polymorphisms in Chinese Patients with Inflammatory Bowel Disease

Thiopurine Methyltransferase Gene Polymorphisms in Chinese Patients with Inflammatory Bowel Disease

Mercaptopurine treatment should be considered in azathioprine intolerant patients with inflammatory bowel disease

Microfluidic Platform for Single Nucleotide Polymorphism Genotyping of the Thiopurine S-Methyltransferase Gene to Evaluate Risk for Adverse Drug Events

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