Typhoid fever and genetic polymorphisms at the natural resistance - Associated macrophage protein 1

Control of Salmonella enterica serovar Typhimurium (S. typhimurium) infecti on in the mouse model of typhoid fever is critically dependent on the natur al resistance- associated macrophage protein 1 (Nramp1). In this study, we examined the role of genetic polymorphisms in the human homologue, NRAMP1, in resistance to typhoid fever in southern Vietnam. Patients with blood- cu lture- confirmed typhoid fever and healthy control subjects were genotyped for 6 polymorphic markers within and near NRAMP1 on chromosome 2q35. Four s ingle base- pair polymorphisms (274 C/ T, 469+ 14 G/ C, 1465-85 G/A, and D5 43N), a (GT)(n) repeat in the promoter region of NRAMP1 and D2S1471, and a microsatellite marker similar to 130-kb downstream of NRAMP1 were examined. The allelic and genotypic frequencies for each polymorphism were compared in case patients and control subjects. No allelic association was identifie d between the NRAMP1 alleles and typhoid fever susceptibility. In addition, neither homozygotes nor heterozygotes for any NRAMP1 variants were at incr eased risk of typhoid fever.