Abstract
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.
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Acknowledgments
We thank Steve Jones, Tudor Parfitt, H. Babiker, Pat Smith, David Zeitlyn, Matthew Forka and Elizabeth Caldwell for help with collection of samples, and Ranji Araseratnam, Abigail Jones and many undergraduate students, in particular Naser Ansari Pour, Fiona Pring and Rhonda Sturley for preparing the DNA and/or testing for LCT markers. C. J. E. Ingram was funded by a BBSRC CASE studentship.
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Ingram, C.J.E., Elamin, M.F., Mulcare, C.A. et al. A novel polymorphism associated with lactose tolerance in Africa: multiple causes for lactase persistence?. Hum Genet 120, 779–788 (2007). https://doi.org/10.1007/s00439-006-0291-1
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DOI: https://doi.org/10.1007/s00439-006-0291-1