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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Expression of the SLC11A1 (NRAMP1) 5′-(GT)
n
repeat: Opposite effect in the presence of -237C→T
Blood Cells, Molecules, and Diseases, Volume 33, No. 1, Year 2004
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Description
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-γ, 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. © 2004 Elsevier Inc. All rights reserved.
Authors & Co-Authors
Zaahl, Monique G.
South Africa, Stellenbosch
Stellenbosch University
United Kingdom, Oxford
John Radcliffe Hospital
South Africa, Cape Town
Stellenbosch University, Faculty of Medicine and Health Sciences
Robson, Kathryn J.H.
United Kingdom, Oxford
John Radcliffe Hospital
Warnich, Louise
South Africa, Stellenbosch
Stellenbosch University
Kotze, Maritha J.
South Africa, Cape Town
Stellenbosch University, Faculty of Medicine and Health Sciences
South Africa, Cape Town
Christiaan Barnard Memorial Hospital
Statistics
Citations: 51
Authors: 4
Affiliations: 4
Identifiers
Doi:
10.1016/j.bcmd.2004.04.003
ISSN:
10799796
Research Areas
Cancer
Genetics And Genomics
Study Design
Cross Sectional Study