Microfluidic platform for single nucleotide polymorphism genotyping of the thiopurine S-methyltransferase gene to evaluate risk for adverse drug events.
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.
Chowdhury
Jeeshan
J
Cross Cancer Institute, 11560 University Ave., Edmonton AB T6G1Z2, Canada.
Kaigala
Govind V
GV
Pushpakom
Sudeep
S
Lauzon
Jana
J
Makin
Alistair
A
Atrazhev
Alexey
A
Stickel
Alex
A
Newman
William G
WG
Backhouse
Christopher J
CJ
Pilarski
Linda M
LM
D019075:Electrophoresis, Capillary; D005838:Genotype; D006801:Humans; D008780:Methyltransferases / Q000235:genetics*; D046208:Microchip Analytical Procedures; D044085:Microfluidics / Q000379:methods*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D013438:Sulfhydryl Compounds / Q000009:adverse effects*
D013438:Sulfhydryl Compounds; D008780:Methyltransferases; C022745:thiopurine methyltransferase
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