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rdf:type |
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lifeskim:mentions |
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pubmed:dateCreated |
2011-6-20
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pubmed:abstractText |
Lactase-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.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:issn |
0065-7778
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
122
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
155-65
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pubmed:meshHeading |
pubmed-meshheading:21686221-African Continental Ancestry Group,
pubmed-meshheading:21686221-Awards and Prizes,
pubmed-meshheading:21686221-Caco-2 Cells,
pubmed-meshheading:21686221-Carbohydrate Metabolism, Inborn Errors,
pubmed-meshheading:21686221-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:21686221-Genetic Predisposition to Disease,
pubmed-meshheading:21686221-Glycosylceramidase,
pubmed-meshheading:21686221-Humans,
pubmed-meshheading:21686221-Hydrolysis,
pubmed-meshheading:21686221-Intestinal Mucosa,
pubmed-meshheading:21686221-Lactase,
pubmed-meshheading:21686221-Lactose,
pubmed-meshheading:21686221-Phenotype,
pubmed-meshheading:21686221-Polymorphism, Single Nucleotide,
pubmed-meshheading:21686221-Promoter Regions, Genetic,
pubmed-meshheading:21686221-Transfection
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pubmed:year |
2011
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pubmed:articleTitle |
Theodore E. Woodward Award: lactase persistence SNPs in African populations regulate promoter activity in intestinal cell culture.
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pubmed:affiliation |
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
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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