Association of typhoid fever severity with polymorphisms NOD2, VDR and NRAMP1 Genes in endemic area, Indonesia

Abstract

Only small proportions of Salmonella enterica serovar Typhi (S. Typhi), in endemic areas, exposing individuals develop typhoid fever symptoms. Identification of polymorphisms NOD2, VDR and NRAMP1 genes is mandatory for a better understanding of typhoid fever molecular pathogenesis and thus to the development of novel strategies for the prevention of infection. The aim of this study was to determine whether genetic polymorphisms in nucleotide oligomerization binding domain 2 (NOD2), vitamin D receptor (VDR) gene and natural resistance-associated macrophage protein 1 (NRAMP1) genes are involved in host susceptibility to severity of typhoid fever. The genotyping of eight regions were applied in the genes; NOD2, VDR and NRAMP1, using PCR-RFLP. A multivariate analysis on 426 mild and 35 severe state of typhoid fever patients. All patients living in the geographically isolated village of South Sulawesi, Middle Sulawesi, Southeast Sulawesi, East Borneo and Papua islands which was an endemic areas in Indonesia. Data were analyzed using Microsoft Excel and Stata 9.2. The G/C and C/C alleles of exon 8 in NOD2 gene were strongly associated and more frequently found in the patients with severe typhoid fever than in mild typhoid fever (p= 0.027and 0.014, odds ratio = 16.7and 27.9, 95% confidence interval = 3.4 -25.7and 2.6 -37.1in G/C allele and C/C allele), respectively. In contrast, No evidence for the association of VDR and NRAMP1 genes polymorphisms with severity state of typhoid fever. The polymorphism of exon 8 in NOD2 gene; heterozygotes or homozygotes for a G6C change in codon 2722, was related to susceptibility to typhoid fever in clinical severity of this disease. Polymorphisms of exon 8 in NOD2 gene; heterozygotes or homozygotes for G/C in codon 2722 were related to susceptibility to typhoid fever in clinical severity.

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