Alternative methods to a TaqMan assay to detect a tri-allelic single nucleotide polymorphism rs757210 in the HNF1β gene

Clin Chem Lab Med. 2011 Oct 21;50(2):279-84. doi: 10.1515/CCLM.2011.758.

Abstract

Background: Several studies report difficulties in genotyping HNF1β rs757210 using TaqMan probes. This is possibly due to the tri-allelic nature of this single nucleotide polymorphism (SNP). The aim of the present research was to develop alternative methods for genotyping rs757210.

Methods: Pyrosequencing and high resolution melting analysis of small amplicons (HRM) were developed and tested in panels of type 2 diabetes mellitus patients (n=258) and healthy blood donors (n=183). Results were confirmed by Sanger sequencing.

Results: With pyrosequencing, allele frequencies for the A, G and C allele of 0.42, 0.56, 0.02 and 0.37, 0.62, 0.01 were established in the panel of type 2 diabetes mellitus patients and healthy blood donors, respectively. Similar results were found using the more routinely available HRM method. Results for pyrosequencing and HRM were in 99.6% concordance.

Conclusions: Pyrosequencing and HRM can be used to genotype the tri-allelic SNP rs757210 in the HNF1β gene and have the advantage over the commercially available TaqMan analysis that they can determine the rare C-allele variant.

MeSH terms

  • Alleles*
  • Female
  • Genotyping Techniques*
  • Hepatocyte Nuclear Factor 1-beta / genetics*
  • Hot Temperature
  • Humans
  • Male
  • Polymorphism, Single Nucleotide*

Substances

  • HNF1B protein, human
  • Hepatocyte Nuclear Factor 1-beta