Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition Stanford University School of Medicine, 300 Pasteur Drive, G310, Stanford, CA 94305, USA. eric.sibley@stanford.edu
Transactions of the American Clinical and Climatological Association 2011Lactase-phlorizin hydrolase, lactase, is the intestinal enzyme responsible for the digestion of the milk sugar lactose. The majority of the world's human population experiences a decline in expression of the lactase gene by late childhood (lactase non-persistence). Individuals with lactase persistence, however, continue to express high levels of the lactase gene throughout adulthood. Lactase persistence is a heritable autosomal dominant condition and has been strongly correlated with several single nucleotide polymorphisms (SNPs) located ∼14 kb upstream of the lactase gene in different ethnic populations: -13910*T in Europeans and -13907*G, -13915*G, and -14010*C in several African populations. The coincidence of the four SNPs clustering within 100 bp strongly suggests that this region mediates the lactase non-persistence/persistence phenotype. Having previously characterized the European SNP, we aimed to determine whether the African SNPs similarly mediate a functional role in regulating the lactase promoter. Human intestinal Caco-2 cells were transfected with lactase SNP/promoter-reporter constructs and assayed for promoter activity. The -13907*G and -13915*G SNPs result in a significant enhancement of lactase promoter activity relative to the ancestral lactase non-persistence genotype. Such differential regulation by the SNPs is consistent with a causative role in the mechanism specifying the lactase persistence phenotype.
Eric Sibley, Jong Kun Ahn. Theodore E. Woodward Award: lactase persistence SNPs in African populations regulate promoter activity in intestinal cell culture. Transactions of the American Clinical and Climatological Association. 2011;122:155-65
PMID: 21686221
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