T-13910 DNA variant associated with lactase persistence interacts with Oct-1 and stimulates lactase promoter activity in vitro

Hum Mol Genet. 2005 Dec 15;14(24):3945-53. doi: 10.1093/hmg/ddi418. Epub 2005 Nov 21.


Two phenotypes exist in the human population with regard to expression of lactase in adults. Lactase non-persistence (adult-type hypolactasia and lactose intolerance) is characterized by a decline in the expression of lactase-phlorizin hydrolase (LPH) after weaning. In contrast, lactase-persistent individuals have a high LPH throughout their lifespan. Lactase persistence and non-persistence are associated with a T/C polymorphism at position -13,910 upstream the lactase gene. A nuclear factor binds more strongly to the T-13,910 variant associated with lactase persistence than the C-13,910 variant associated with lactase non-persistence. Oct-1 and glyceraldehyde-3-phosphate dehydrogenase were co-purified by DNA affinity purification using the sequence of the T-13,910 variant. Supershift analyses show that Oct-1 binds directly to the T-13,910 variant, and we suggest that GAPDH is co-purified due to interactions with Oct-1. Expression of Oct-1 stimulates reporter gene expression from the T and the C-13,910 variant/LPH promoter constructs only when it is co-expressed with HNF1alpha. Binding sites for other intestinal transcription factors (GATA-6, HNF4alpha, Fox and Cdx-2) were identified in the region of the -13,910 T/C polymorphism. Three of these sites are required for the enhancer activity of the -13,910 region. The data suggest that the binding of Oct-1 to the T-13,910 variant directs increased lactase promoter activity and this might provide an explanation for the lactase persistence phenotype in the human population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Enhancer Elements, Genetic
  • Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+) / genetics
  • Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+) / isolation & purification
  • Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+) / metabolism
  • Hepatocyte Nuclear Factor 1-alpha / genetics
  • Hepatocyte Nuclear Factor 1-alpha / metabolism
  • Humans
  • Lactase / genetics*
  • Lactase / metabolism
  • Lactase-Phlorizin Hydrolase / genetics
  • Lactase-Phlorizin Hydrolase / metabolism
  • Lactose Intolerance / genetics
  • Octamer Transcription Factor-1 / genetics
  • Octamer Transcription Factor-1 / metabolism*
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic / genetics*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • Hepatocyte Nuclear Factor 1-alpha
  • Octamer Transcription Factor-1
  • Transcription Factors
  • Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+)
  • Lactase
  • Lactase-Phlorizin Hydrolase