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Comparative Study
. 2001 Apr 1;183(7):1156-60.
doi: 10.1086/319289. Epub 2001 Mar 1.

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

S J Dunstan  1 , V A Ho, C M Duc, M N Lanh, C X Phuong, C Luxemburger, J Wain, F Dudbridge, C S Peacock, D House, C Parry, T T Hien, G Dougan, J Farrar, J M Blackwell
Affiliations
Comparative Study

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

S J Dunstan et al. J Infect Dis. .

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)(n) repeat in the promoter region of NRAMP1 and D2S1471, and a microsatellite marker approximately 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 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.

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Figures

Figure 1
Figure 1
Typhoid patients and controls were genotyped for six polymorphisms within and near NRAMP1. This schematic representation shows the location of the polymorphisms genotyped. Four intragenic NRAMP1 polymorhisms (274C/T, 469+14G/C, 1465-85G/A and D543N), one polymorphism in the promoter region of NRAMP1 ([GT]n) and the microsatellite marker D2S1471 were genotyped. The overall allele frequencies of the six individual markers in typhoid cases and controls were compared by the likelihood ratio test. Maximum likelihood frequencies of the possible haplotypes of the 5′ markers, the 3′ markers and all markers across the gene region were estimated using the E-M algorithm. Below the tests for the individual markers are bars that represent the various 2, 3, 5 and 6 loci haplotypes tested. The overall frequencies of the estimated haplotypes were compared in typhoid cases and controls. Empirical P values are stated.
See this image and copyright information in PMC

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