The influence of host and bacterial genotype on the development of disseminated disease with Mycobacterium tuberculosis - PubMed (original) (raw)

. 2008 Mar 28;4(3):e1000034.

doi: 10.1371/journal.ppat.1000034.

Guy Thwaites, Sarah Dunstan, Thomas R Hawn, Nguyen Thi Ngoc Lan, Nguyen Thuy Thuong Thuong, Kasia Stepniewska, Mai Nguyet Thu Huyen, Nguyen Duc Bang, Tran Huu Loc, Sebastien Gagneux, Dick van Soolingen, Kristin Kremer, Marianne van der Sande, Peter Small, Phan Thi Hoang Anh, Nguyen Tran Chinh, Hoang Thi Quy, Nguyen Thi Hong Duyen, Dau Quang Tho, Nguyen T Hieu, Estee Torok, Tran Tinh Hien, Nguyen Huy Dung, Nguyen Thi Quynh Nhu, Phan Minh Duy, Nguyen van Vinh Chau, Jeremy Farrar

Affiliations

The influence of host and bacterial genotype on the development of disseminated disease with Mycobacterium tuberculosis

Maxine Caws et al. PLoS Pathog. 2008.

Abstract

The factors that govern the development of tuberculosis disease are incompletely understood. We hypothesized that some strains of Mycobacterium tuberculosis (M. tuberculosis) are more capable of causing disseminated disease than others and may be associated with polymorphisms in host genes responsible for the innate immune response to infection. We compared the host and bacterial genotype in 187 Vietnamese adults with tuberculous meningitis (TBM) and 237 Vietnamese adults with uncomplicated pulmonary tuberculosis. The host genotype of tuberculosis cases was also compared with the genotype of 392 cord blood controls from the same population. Isolates of M. tuberculosis were genotyped by large sequence polymorphisms. The hosts were defined by polymorphisms in genes encoding Toll-interleukin 1 receptor domain containing adaptor protein (TIRAP) and Toll-like receptor-2 (TLR-2). We found a significant protective association between the Euro-American lineage of M. tuberculosis and pulmonary rather than meningeal tuberculosis (Odds ratio (OR) for causing TBM 0.395, 95% confidence intervals (C.I.) 0.193-0.806, P = 0.009), suggesting these strains are less capable of extra-pulmonary dissemination than others in the study population. We also found that individuals with the C allele of TLR-2 T597C allele were more likely to have tuberculosis caused by the East-Asian/Beijing genotype (OR = 1.57 [95% C.I. 1.15-2.15]) than other individuals. The study provides evidence that M. tuberculosis genotype influences clinical disease phenotype and demonstrates, for the first time, a significant interaction between host and bacterial genotypes and the development of tuberculosis.

PubMed Disclaimer

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1

Figure 1. Mycobacterium tuberculosis lineages defined by large sequence polymorphism (LSP) analysis.

The circles represent Region of difference (RD region) deleted in each lineage. Only East Asian, Indo-Oceanic and Euro-American lineages were identified in Vietnam.

Similar articles

Cited by

References

    1. Selwyn PA, Alcabes P, Hartel D, Buono D, Schoenbaum EE, et al. Clinical manifestations and predictors of disease progression in drug users with human immunodeficiency virus infection. N Engl J Med. 1992;327:1697–1703. - PubMed
    1. Fitness J, Floyd S, Warndorff DK, Sichali L, Malema S, et al. Large-scale candidate gene study of tuberculosis susceptibility in the Karonga district of northern Malawi. Am J Trop Med Hyg. 2004;71:341–349. - PubMed
    1. Shaw MA, Collins A, Peacock CS, Miller EN, Black GF, et al. Evidence that genetic susceptibility to Mycobacterium tuberculosis in a Brazilian population is under oligogenic control: linkage study of the candidate genes NRAMP1 and TNFA. Tuber Lung Dis. 1997;78:35–45. - PubMed
    1. Gao PS, Fujishima S, Mao XQ, Remus N, Kanda M, et al. Genetic variants of NRAMP1 and active tuberculosis in Japanese populations. International Tuberculosis Genetics Team. Clin Genet. 2000;58:74–76. - PubMed
    1. Bellamy R, Ruwende C, Corrah T, McAdam KP, Whittle HC, et al. Variations in the NRAMP1 gene and susceptibility to tuberculosis in West Africans. N Engl J Med. 1998;338:640–644. - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources