Microfluidic platform for single nucleotide polymorphism genotyping of the thiopurine S-methyltransferase gene to evaluate risk for adverse drug events

J Mol Diagn. 2007 Sep;9(4):521-9. doi: 10.2353/jmoldx.2007.070014. Epub 2007 Aug 9.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Electrophoresis, Capillary
  • Genotype
  • Humans
  • Methyltransferases / genetics*
  • Microchip Analytical Procedures
  • Microfluidics / methods*
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single Nucleotide / genetics*
  • Risk Factors
  • Sulfhydryl Compounds / adverse effects*

Substances

  • Sulfhydryl Compounds
  • Methyltransferases
  • thiopurine methyltransferase