1. Microfluidic Platform for Single Nucleotide Polymorphism Genotyping of the Thiopurine S-Methyltransferase Gene to Evaluate Risk for Adverse Drug Events
- Author
-
Jeeshan Chowdhury, Christopher J. Backhouse, Alexey Atrazhev, Jana Lauzon, Linda M. Pilarski, Alistair J Makin, Alex Stickel, Govind V. Kagiala, Sudeep Pushpakom, and William G. Newman
- Subjects
Thiopurine methyltransferase ,biology ,Cost effectiveness ,Single-nucleotide polymorphism ,Bioinformatics ,Pathology and Forensic Medicine ,law.invention ,law ,Genotype ,biology.protein ,Molecular Medicine ,Restriction fragment length polymorphism ,Genotyping ,Polymerase chain reaction ,Pharmacogenetics - Abstract
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 microchip-based 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.
- Published
- 2007