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

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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.

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Abbreviations

LCT :

Lactase gene

LPH:

Lactase-phlorizin hydrolase

LP:

Lactase persistence

LNP:

Lactase non-persistence

MCM6 :

Minichromosome maintenance 6 gene

SNP:

Single nucleotide polymorphism

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Acknowledgments

We thank Lotte Bram for excellent technical assistance. This work was supported by the Lundbeck Foundation, the Augustinus Foundation, Aase and Ejnar Danielsen Foundation, the Danish Research Council and EU FP7 ITN Grant 215362-2 (LeCHE).

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Authors and Affiliations

  1. Department of Cellular and Molecular Medicine, Panum Institute, Building 6.4, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen N, Denmark

    Tine G. K. Jensen, Rikke Lewinsky, Jørgen Olsen & Jesper T. Troelsen

  2. Research Department of Genetics, Evolution and Environment, University College London, London, NW1 2HE, UK

    Anke Liebert & Dallas M. Swallow

  3. Department of Sciences, Systems and Models, University of Roskilde, Universitetsvej 1, 4000, Roskilde, Denmark

    Jesper T. Troelsen

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  1. Tine G. K. Jensen
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  2. Anke Liebert
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  3. Rikke Lewinsky
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  4. Dallas M. Swallow
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  5. Jørgen Olsen
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  6. Jesper T. Troelsen
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Correspondence to Jesper T. Troelsen.

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Jensen, T.G.K., Liebert, A., Lewinsky, R. et al. The −14010*C variant associated with lactase persistence is located between an Oct-1 and HNF1α binding site and increases lactase promoter activity. Hum Genet 130, 483–493 (2011). https://doi.org/10.1007/s00439-011-0966-0

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  • DOI: https://doi.org/10.1007/s00439-011-0966-0

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