High-throughput genotyping of copy number variation in glutathione S-transferases M1 and T1 using real-time PCR in 20,687 individuals

Clin Biochem. 2009 Feb;42(3):201-9. doi: 10.1016/j.clinbiochem.2008.10.020. Epub 2008 Nov 7.

Abstract

Objectives: Characteristic for the genes encoding glutathione S-transferase (GST) M1 and GSTT1 is a null allele, suggested to increase susceptibility to chronic diseases. We report an optimized method for the determination of copy number variation (CNV) in GST genes.

Design and methods: Real-time multiplex PCR reactions were optimized for quantification of GSTM1 and GSTT1 CNV using the DeltaCt method, a fixed volume of diluted DNA, a total volume of 10 microL, 384-well formats, and single determinations of each sample.

Results: Consistent genotyping was obtained using DNA in a range of 0.41 ng to 100 ng. In a general population sample of 20,687 individuals the genotype frequencies were concordant with other methods used as standards. Throughput was 4600 genotypes per day at a reagent price of 0.5 euros per sample.

Conclusions: This high-throughput, low cost method accurately determines CNV in the GST genes enabling reliable estimates of disease prediction in large epidemiological samples.

MeSH terms

  • Gene Dosage*
  • Gene Frequency
  • Genotype
  • Glutathione Transferase / genetics*
  • Humans
  • Mass Screening
  • Molecular Epidemiology / methods*
  • Polymerase Chain Reaction / methods*

Substances

  • glutathione S-transferase T1
  • Glutathione Transferase
  • glutathione S-transferase M1