Human Genetics

, Volume 131, Issue 7, pp 1153–1159

The human lactase persistence-associated SNP −13910*T enables in vivo functional persistence of lactase promoter–reporter transgene expression

  • Lin Fang
  • Jong Kun Ahn
  • Dariusz Wodziak
  • Eric Sibley
Original Investigation

DOI: 10.1007/s00439-012-1140-z

Cite this article as:
Fang, L., Ahn, J.K., Wodziak, D. et al. Hum Genet (2012) 131: 1153. doi:10.1007/s00439-012-1140-z

Abstract

Lactase is the intestinal enzyme responsible for digestion of the milk sugar lactose. Lactase gene expression declines dramatically upon weaning in mammals and during early childhood in humans (lactase nonpersistence). In various ethnic groups, however, lactase persists in high levels throughout adulthood (lactase persistence). Genetic association studies have identified that lactase persistence in northern Europeans is strongly associated with a single nucleotide polymorphism (SNP) located 14 kb upstream of the lactase gene: −13910*C/T. To determine whether the −13910*T SNP can function in vivo to mediate lactase persistence, we generated transgenic mice harboring human DNA fragments with the −13910*T SNP or the ancestral −13910*C SNP cloned upstream of a 2-kb rat lactase gene promoter in a luciferase reporter construct. We previously reported that the 2-kb rat lactase promoter directs a post-weaning decline of luciferase transgene expression similar to that of the endogenous lactase gene. In the present study, the post-weaning decline directed by the rat lactase promoter is impeded by addition of the −13910*T SNP human DNA fragment, but not by addition of the −13910*C ancestral SNP fragment. Persistence of transgene expression associated with the −13910*T SNP represents the first in vivo data in support of a functional role for the −13910*T SNP in mediating the human lactase persistence phenotype.

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Lin Fang
    • 1
  • Jong Kun Ahn
    • 1
  • Dariusz Wodziak
    • 1
  • Eric Sibley
    • 1
  1. 1.Department of Pediatrics (Gastroenterology)Stanford University School of MedicineStanfordUSA