Expression of the SLC11A1 (NRAMP1) 5'-(GT)n repeat: opposite effect in the presence of -237C-->T.

摘要: Abstract Association of various autoimmune and infectious diseases with genetic variation in the solute carrier family 11 member 1 ( SLC11A1) gene, formerly known as natural resistance-associated macrophage protein NRAMP1 ) is accordance its role iron metabolism immune function. In this investigation, vitro studies were performed to determine whether allelic variants promoter region gene are affected by loading, thereby leading differential expression SLC11A1 . Constructs containing five different 5′-(GT) n polymorphic alleles identified South African population (alleles 2, 3, 5, 8, 9) a C T point mutation at nucleotide position −237, both absence presence allele cloned into pGL2-Basic luciferase-reporter vector transfected U937 THP-1 cells. Addition exogenous stimuli, including interferon-γ, bacterial lipopolysaccharide, ferric ammonium citrate, demonstrated significant differences ability these regulate expression. Striking obtained upon 3 showing opposite effects or polymorphism −237C→T. Our findings provide direct evidence that functional support hypothesis dysregulation mediated underlies disease susceptibility linked conditions.