A novel polymorphism associated with lactose tolerance in Africa: multiple causes for lactase persistence?

Hum Genet. 2007 Feb;120(6):779-88. doi: 10.1007/s00439-006-0291-1. Epub 2006 Nov 21.


Persistence or non-persistence of lactase expression into adult life is a polymorphic trait that has been attributed to a single nucleotide polymorphism (C-13910T) in an enhancer element 13.9 kb upstream of the lactase gene (LCT). The -13910*T allele occurs at very high frequency in northern Europeans as part of a very long haplotype (known as A), and promotes binding of the transcription factor Oct-1. However, -13910*T is at very low frequency in many African milk drinking pastoralist groups where lactase persistence phenotype has been reported at high frequency. We report here for the first time, a cohort study of lactose digester and non-digester Sudanese volunteers and show there is no association of -13910*T or the A haplotype with lactase persistence. We support this finding with new genotype/phenotype frequency comparisons in pastoralist groups of eastern African and Middle Eastern origin. Resequencing revealed three new SNPs in close proximity to -13910*T, two of which are within the Oct-1 binding site. The most frequent of these (-13915*G) is associated with lactose tolerance in the cohort study, providing evidence for a cis-acting effect. Despite its location, -13915*G abolishes, rather than enhances Oct-1 binding, indicating that this particular interaction is unlikely to be involved in lactase persistence. This study reveals the complexity of this phenotypic polymorphism and highlights the limitations of C-13910T as a diagnostic test for lactase persistence status, at least for people with non-European ancestry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Africa
  • Base Sequence
  • Binding Sites / genetics
  • Cohort Studies
  • DNA / genetics
  • DNA / metabolism
  • DNA Probes / genetics
  • Enhancer Elements, Genetic
  • Ethnic Groups / genetics
  • Gene Frequency
  • Genotype
  • Haplotypes
  • Humans
  • Introns
  • Lactase / genetics*
  • Lactose Intolerance / enzymology*
  • Lactose Intolerance / genetics*
  • Middle East
  • Octamer Transcription Factor-1 / metabolism
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Sequence Homology, Nucleic Acid


  • DNA Probes
  • Octamer Transcription Factor-1
  • DNA
  • Lactase