Linked Life Data

15223010

Source:http://linkedlifedata.com/resource/pubmed/id/15223010

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-6-29
pubmed:abstractText
Association of various autoimmune and infectious diseases with genetic variation in the solute carrier family 11 member 1 (SLC11A1) gene, formerly known as the natural resistance-associated macrophage protein 1 (NRAMP1) gene, is in accordance with its role in iron metabolism and immune function. In this investigation, in vitro studies were performed to determine whether allelic variants in the promoter region of the gene are affected by iron loading, thereby leading to differential expression of SLC11A1. Constructs containing five different SLC11A1 5'-(GT)n polymorphic alleles identified in the South African population (alleles 2, 3, 5, 8, and 9) and a C to T point mutation at nucleotide position -237, both in the absence and presence of allele 3, were cloned into the pGL2-Basic luciferase-reporter vector and transfected into U937 and THP-1 cells. Addition of exogenous stimuli, including interferon-gamma, bacterial lipopolysaccharide, and ferric ammonium citrate, demonstrated significant differences in the ability of these alleles to regulate gene expression. Striking differences were obtained upon iron loading, with allele 3 showing opposite effects in the presence or absence of promoter polymorphism -237C-->T. Our findings provide direct evidence that this promoter polymorphism is functional and support the hypothesis that iron dysregulation mediated by allelic effects of SLC11A1 underlies disease susceptibility linked to infectious and autoimmune conditions.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1079-9796
pubmed:author
pubmed:issnType
Print
pubmed:volume
33
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
45-50
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:articleTitle
Expression of the SLC11A1 (NRAMP1) 5'-(GT)n repeat: opposite effect in the presence of -237C-->T.
pubmed:affiliation
Department of Genetics, University of Stellenbosch, Stellenbosch, South Africa. mjulies@sun.ac.za
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't