Functional analysis of novel SLC11A1 (NRAMP1) promoter variants in susceptibility to HIV-1

Donninger, H.
Cashmore, T. J.
Scriba, T.
Petersen, D. C.
Janse Van Rensburg, E.
Hayes, V. M.
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BMJ Publishing Group
The divalent cation transporter is the natural resistance associated macrophage protein 1 (formerly NRAMP1 and now named SLC11A1) for solute carrier 11A1 (OMIM accession number 600266). The gene that codes for this transporter has been studied intensively for its role in conferring susceptibility to infectious diseases such as tuberculosis, leprosy, meningococcal meningitis, visceral leishmaniasis, and HIV infection, as well as to autoimmune diseases such as rheumatoid arthritis, diabetes, sarcoidosis, inflammatory bowel disease,1 and, more recently, Kawasaki disease.2 Most studies have investigated a functional GT repeat sequence in the promoter region of this gene3 and have identified two commonly occurring repeat alleles and four rare repeat alleles.4,5 The common alleles are T(GT)5AC(GT)5AC(GT)10 (allele 2) and T(GT)5AC(GT)5AC(GT)9 (allele 3; GenBank accession number AF229163, 5768 to 5808). Allele 2, which decreases gene expression, has been associated with susceptibility to infectious diseases; the more common allele 3 enhances gene expression to protect against infectious diseases while enhancing susceptibility to autoimmune diseases. Although HIV is classified as an infectious disease, it affects the autoimmune system, which may explain why allele 3 is associated with susceptibility to HIV-1.6,7 This study aimed to screen the promoter region of SLC11A1 for novel sequence variations in people from sub-Saharan Africa infected with HIV-1 compared with uninfected people and to determine the effect of novel variants on normal promoter function.
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DNA mutational analysis, Genetic predisposition to disease, HIV Infections, HIV-1, Molecular sequence data
Donninger, H. et al. 2004. Functional analysis of novel SLC11A1 (NRAMP1) promoter variants in susceptibility to HIV-1. J. Med. Genet., 41(4):e49 doi:10.1136/jmg.2003.013318.