Published online before print August 9, 2007

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Copyright © 2007 American Society for Investigative Pathology
Journal of Molecular Diagnostics, doi:10.2353/jmoldx.2007.070014

Accepted for publication April 13, 2007.

Article

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

Jeeshan Chowdhury^*, Govind V. Kagiala, Sudeep Pushpakom, Jana Lauzon^*, Alistair Makin, Alexey Atrazhev^*, Alex Stickel, William G. Newman, Christopher J. Backhouse, and Linda M. Pilarski^*@

From the Department of Oncology,* Cross Cancer Institute, Edmonton, Canada; the Applied Miniaturization Laboratory, Electrical and Computer Engineering, University of Alberta, Edmonton, Canada; the Academic Unit of Medical Genetics, University of Manchester, St. Mary's Hospital, Manchester, United Kingdom; and the Department of Gastroenterology, Manchester Royal Infirmary, Manchester, United Kingdom

^@ To whom correspondence should be addressed. E-mail: lpilarsk{at}ualberta.ca.

	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.