Genetic association studies have identified several polymorphisms in genes of the innate immunity cascade that appear to influence susceptibility to asthma and other inflammatory diseases. However, most candidate genes have not been functionally characterized for their impact on human immune responsiveness. An excellent candidate for functional investigation is NFKBIA which encodes IκBα--the major negative regulator of NFκB. Single nucleotide polymorphisms (SNPs) in the promoter region of NFKBIA have been implicated in various infectious and inflammatory diseases. Specifically, the linked promoter SNPs rs2233406, rs3138053 and rs2233409 have been implicated in sarcoidosis, trachoma, acute respiratory distress syndrome, invasive pneumococcal disease, Graves' disease and respiratory syncytial virus. We investigated the mechanistic and functional impact of the promoter variants of NFKBIA on human immune responsiveness.