Genes of the Class II and Class III Major Histocompatibility Complex Are Associated with Typhoid Fever in Vietnam

Abstract

The influence of genes of the major histocompatibility complex (MHC) class II and class III loci on typhoid fever susceptibility was investigated. Individuals with blood culture-confirmed typhoid fever and control subjects from 2 distinct geographic locations in southern Vietnam were genotyped for HLA-DRB1 and HLA-DQB1 alleles, the gene that encodes tumor necrosis factor (TNF)-alpha (TNFA [-238] and TNFA [-308]), the gene that encodes lymphotoxin-alpha, and alleles of the TNF-alpha microsatellite. HLA-DRB1*0301/6/8, HLA-DQB1*0201-3, and TNFA*2 (-308) were associated with susceptibility to typhoid fever, whereas HLA-DRB1*04, HLA-DQB1*0401/2, and TNFA*1 (-308) were associated with disease resistance. The frequency of all possible haplotypes of the 3 individually associated loci were estimated and were found to be significantly different in typhoid case patients and control subjects (chi2=55.56, 32 df; P=.006). Haplotypes that were either protective (TNFA*1 [-308].DRB1*04) or predisposed individuals to typhoid fever (TNFA*2 [-308].DRB1*0301) were determined. This report identifies a genetic association in humans between typhoid fever and MHC class II and III genes.

Atopy in children in relation to BCG vaccination and genetic polymorphisms at SLC11A1 (formerly NRAMP1) and D2S1471

“…However, given that a strong association is only observed in the BCG vaccinated group, and that SLC11A1 is known to regulate immune response to mycobacterial infection and vaccination, it seems more likely that the association observed is due to linkage disequilibrium between D2S1471 and 3Ј haplotypes in SLC11A1. This is consistent with previous work 40 in a Vietnamese population, where no linkage disequilibrium was observed between 5Ј and 3Ј polymorphic markers within the SLC11A1 locus, but evidence was obtained for linkage disequilibrium between 3Ј SLC11A1 markers and D2S1471. Also with the demonstration that both 5Ј and 3Ј polymorphisms at SLC11A1 are independently associated with susceptibility to tuberculosis in the Gambia, 17 indicating that there are likely to be as yet unidentified functional polymorphisms at the 3Ј end of the SLC11A1 gene.…”

A TNF region haplotype offers protection from typhoid fever in Vietnamese patients

“…Venous blood (2 ml) was collected from 380 patients with blood culture positive typhoid fever admitted to one of the three hospitals. The samples and studies have been described previously (Chinh et al 2000;Dunstan et al 2001;Luxemburger et al 2001;Phuong et al 1999;Vinh et al 2004). In addition umbilical cord blood samples from babies born at Huong Vuong Hospital in Ho Chi Minh City were collected.…”

Genetic regulation of host responses to Salmonella infection in mice

“…Class II MHC was shown to be associated with susceptibility to Salmonella Typhi in Vietnam where typhoid fever is endemic, 37 and MHC class Ib molecules were associated with the development of autoimmune reactive arthritis following Salmonella infection. 38,39 The inherent complexity and polymorphism of the MHC complex and the linkage disequilibrium between loci will continue to pose a significant challenge to the identification of specific Salmonella susceptibility genes located in this area of the genome.…”