title: The influence of host and bacterial genotype on the development of disseminated disease with Mycobacterium tuberculosis.
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.
authors: Oxford University Clinical Research Unit, Hospital for Tropical Diseases, District 5, Ho Chi Minh City, Vietnam. mcaws@hotmail.com
authors: Maxine
authors: M
authors: Caws
authors: Guy
authors: G
authors: Thwaites
authors: Sarah
authors: S
authors: Dunstan
authors: Thomas R
authors: TR
authors: Hawn
authors: Nguyen Thi Ngoc
authors: NT
authors: Lan
authors: Nguyen Thuy Thuong
authors: NT
authors: Thuong
authors: Kasia
authors: K
authors: Stepniewska
authors: Mai Nguyet Thu
authors: MN
authors: Huyen
authors: Nguyen Duc
authors: ND
authors: Bang
authors: Tran Huu
authors: TH
authors: Loc
authors: Sebastien
authors: S
authors: Gagneux
authors: Dick
authors: D
authors: van Soolingen
authors: Kristin
authors: K
authors: Kremer
authors: Marianne
authors: M
authors: van der Sande
authors: Peter
authors: P
authors: Small
authors: Phan Thi Hoang
authors: PT
authors: Anh
authors: Nguyen Tran
authors: NT
authors: Chinh
authors: Hoang Thi
authors: HT
authors: Quy
authors: Nguyen Thi Hong
authors: NT
authors: Duyen
authors: Dau Quang
authors: DQ
authors: Tho
authors: Nguyen T
authors: NT
authors: Hieu
authors: Estee
authors: E
authors: Torok
authors: Tran Tinh
authors: TT
authors: Hien
authors: Nguyen Huy
authors: NH
authors: Dung
authors: Nguyen Thi Quynh
authors: NT
authors: Nhu
authors: Phan Minh
authors: PM
authors: Duy
authors: Nguyen
authors: N
authors: van Vinh Chau
authors: Jeremy
authors: J
authors: Farrar
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D005798:Genes, Bacterial; D020022:Genetic Predisposition to Disease; D005838:Genotype; D054884:Host-Pathogen Interactions / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity; D020641:Polymorphism, Single Nucleotide; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism; D014390:Tuberculosis, Meningeal / Q000235:genetics / Q000276:immunology / Q000382:microbiology*; D014397:Tuberculosis, Pulmonary / Q000235:genetics / Q000276:immunology / Q000382:microbiology*; D014744:Vietnam
chemical_list: D051195:Toll-Like Receptor 2