Original Investigation

Human Genetics

, Volume 130, Issue 4, pp 483-493

The −14010*C variant associated with lactase persistence is located between an Oct-1 and HNF1α binding site and increases lactase promoter activity

  • Tine G. K. JensenAffiliated withDepartment of Cellular and Molecular Medicine, Panum Institute, Building 6.4, University of Copenhagen
  • , Anke LiebertAffiliated withResearch Department of Genetics, Evolution and Environment, University College London
  • , Rikke LewinskyAffiliated withDepartment of Cellular and Molecular Medicine, Panum Institute, Building 6.4, University of Copenhagen
  • , Dallas M. SwallowAffiliated withResearch Department of Genetics, Evolution and Environment, University College London
  • , Jørgen OlsenAffiliated withDepartment of Cellular and Molecular Medicine, Panum Institute, Building 6.4, University of Copenhagen
  • , Jesper T. TroelsenAffiliated withDepartment of Cellular and Molecular Medicine, Panum Institute, Building 6.4, University of CopenhagenDepartment of Sciences, Systems and Models, University of Roskilde Email author 

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Abstract

In most people worldwide intestinal lactase expression declines in childhood. In many others, particularly in Europeans, lactase expression persists into adult life. The lactase persistence phenotype is in Europe associated with the −13910*T single nucleotide variant located 13,910 bp upstream the lactase gene in an enhancer region that affects lactase promoter activity. This variant falls in an Oct-1 binding site and shows greater Oct-1 binding than the ancestral variant and increases enhancer activity. Several other variants have been identified very close to the −13910 position, which are associated with lactase persistence in the Middle East and Africa. One of them, the −14010*C, is associated with lactase persistence in Africa. Here we show by deletion analysis that the −14010 position is located in a 144 bp region that reduces the enhancer activity. In transfections the −14010*C allele shows a stronger enhancer effect than the ancestral −14010*G allele. Binding sites for Oct-1 and HNF1α surrounding the −14010 position were identified by gel shift assays, which indicated that −14010*C has greater binding affinity to Oct-1 than −14010*G.