Linked Life Data

12915462

Source:http://linkedlifedata.com/resource/pubmed/id/12915462

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
2003-9-3
pubmed:abstractText
Lactase persistence is a heritable, autosomal dominant, condition that results in a sustained ability to digest the milk sugar lactose throughout adulthood. The majority of the world's human population experiences a decline in production of the digestive enzyme lactase-phlorizin hydrolase during maturation. However, individuals with lactase persistence continue to express high levels of the lactase gene into adulthood. Lactase persistence has been strongly correlated with single nucleotide genetic variants, C/T_(13910) and G/A_(22018), located 13.9 and 22 kb upstream from the lactase structural gene. We aimed to characterize a functional role for the polymorphisms in regulating lactase gene transcription. DNA in the region of the C/T_(13910) or G/A_(22018) human lactase variants was cloned upstream of the 3.0 kb rat lactase gene promoter in a luciferase reporter construct. Human intestinal Caco-2 cells were transfected with the lactase variant/promoter-reporter constructs and assayed for promoter activity. A 200 bp region surrounding the C_(13910) variant, associated with lactase non-persistence, results in a 2.2-fold increase in lactase promoter activity. The T_(13910) variant, associated with lactase persistence, results in an even greater 2.8-fold increase. The DNA sequence of the C/T_(13910) variants differentially interacts with intestinal cell nuclear proteins on EMSAs. AP2 co-transfection results in a similar repression of the C/T_(13910) variant/promoter-reporter constructs. The DNA region of the C/T_(13910) lactase persistence/non-persistence variant functions in vitro as a cis element capable of enhancing differential transcriptional activation of the lactase promoter. Such differential regulation by the C and T variants is consistent with a causative role in the mechanism specifying the lactase persistence/non-persistence phenotypes in humans.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0964-6906
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2333-40
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:12915462-Base Sequence, pubmed-meshheading:12915462-Caco-2 Cells, pubmed-meshheading:12915462-Cell Nucleus, pubmed-meshheading:12915462-DNA, pubmed-meshheading:12915462-DNA-Binding Proteins, pubmed-meshheading:12915462-Gene Expression Regulation, Enzymologic, pubmed-meshheading:12915462-Genes, pubmed-meshheading:12915462-Genes, Dominant, pubmed-meshheading:12915462-Genes, Reporter, pubmed-meshheading:12915462-Genetic Variation, pubmed-meshheading:12915462-Humans, pubmed-meshheading:12915462-Lactase, pubmed-meshheading:12915462-Lactose Intolerance, pubmed-meshheading:12915462-Luciferases, pubmed-meshheading:12915462-Nuclear Proteins, pubmed-meshheading:12915462-Polymorphism, Genetic, pubmed-meshheading:12915462-Promoter Regions, Genetic, pubmed-meshheading:12915462-Sensitivity and Specificity, pubmed-meshheading:12915462-Transcription Factors, pubmed-meshheading:12915462-Transfection
pubmed:year
2003
pubmed:articleTitle
Lactase persistence DNA variant enhances lactase promoter activity in vitro: functional role as a cis regulatory element.
pubmed:affiliation
Department of Pediatrics, Stanford University School of Medicine, 750 Welch Road, Suite 116, Palo Alto, CA 94305, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.