Identification of C to T mutation at position -236 bp in the human NRAMP1 gene promoter

Susceptibility to infection by agents such as parasites or bacteria has been found in some cases to be under genetic influence. In inbred mice, susceptibility to infection by a number of intracellular parasites including leishmania, mycobacteria, and salmonella can be determined by a single gene, named Bcg/Lsh/Ity, located on chromosome 1. The gene for Bcg has been identified as natural resistance-associated macrophage protein gene (Nramp) which encodes a putative macrophage-specific integral membrane protein. The human homologue NRAMP1 is located on chromosome 2q35 and contains at least 15 exons encoding ten to twelve putative transmembrane domains. The NRAMP1 protein also contains a conserved consensus transport motif and two predicted N-linked glycosylation sites. Polymorphic variants of genes are important in attempting to link genes with susceptibility to disease. Thus, a single base mutation in the coding region of the Nramp gene is thought to be responsible for susceptibility to infectious disease in mice. No equivalent mutation has thus far been detected in the human homologue. A thorough dissection of NRAMP1 is therefore required if polymorphisms are to be used to assess linkage to susceptibility. Mutations (polymorphisms) may result in either structural changes in proteins or alter expression. Polymorphisms with the potential to affect expression have been found in the 3' untranslated region and in the promoter region of NRAMP1. This paper reports a new mutation in the promoter region of the human NRAMP1 gene, which is a C to T substitution at position -236 bp from the transcription start site.