Mutational analysis of the solute carrier family 11 member 1 gene (SLC11A1) implicated in iron transport

[摘要] ENGLISH ABSTRACT:The solute carrier family 11 member 1 gene (SLC11A 1) is a divalent metal iontransporter with various pleiotropic effects on macrophage function. This gene thatregulates iron, and is also regulated by cellular iron levels, has previously been linkedto many infectious and autoimmune diseases. In this analysis, in vitro studies usingthe luciferase reporter system as well as case-control association studies wereapplied to investigate the significance of SLC11 A1 allelic variation in patients withdiverse disease phenotypes.For in vitro studies, five different SLC11A 1 promoter constructs were generated,followed by transfection into U937 and THP-1 cells. The inserted fragments includedtwo previously described alleles (alleles 2 and 3), two novel alleles identified in thisstudy (alleles 8 and 9) and a C to T point mutation at nucleotide position -237 in thepresence of allele 3. The most striking finding was the opposite effect observed forallele 3 in the presence of the -237C~ T polymorphism, similar to that of allele 2.Although the SLC11A 1 gene has previously been implicated in iron transport, wehave demonstrated, for the first time, that the various alleles investigated causedifferential expression of the gene upon iron loading.Association studies were performed by investigating diseases including oesophagealcancer (DC), inflammatory bowel disease (lBO) and hereditary haemochromatosis(HH) (or primary iron overload). Significant associations (P

[发布机构] Stellenbosch University