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

Sarah J. Dunstan, Vo An Ho, Chau Minh Duc, Mai Ngoc Lanh, Cao Xuan Thanh Phuong, Christine Luxemburger, John Wain, Frank Dudbridge, Christopher S. Peacock, Deborah House, Christopher Parry, Tran Tinh Hien, Gordon Dougan, Jeremy Farrar, Jenefer M. Blackwell

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Abstract

Control of Salmonella enterica serovar Typhimurium (S. typhimurium) infection in the mouse model of typhoid fever is critically dependent on the natural 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-culture-confirmed typhoid fever and healthy control subjects were genotyped for 6 polymorphic markers within and near NRAMP1 on chromosome 2q35. Four single base-pair polymorphisms (274 C/T, 469+14 G/C, 1465-85 G/A, and D543N), a (GT)nrepeat in the promoter region of NRAMP1 and D2S1471, and a microsatellite marker ∼130kb 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 identified between the NRAMP1 alleles and typhoid fever susceptibility. In addition, neither homozygotes nor heterozygotes for any NRAMP1 variants were at increased risk of typhoid fever.

Original languageEnglish
Pages (from-to)1156-1160
Number of pages5
JournalThe Journal of Infectious Diseases
Volume183
Issue number7
DOIs
Publication statusPublished - 1 Apr 2001
Externally publishedYes

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