title: TLR9 gene region polymorphisms and susceptibility to tuberculosis in Vietnam.
abstract: Humans exposed to Mycobacterium tuberculosis (Mtb) show variation in susceptibility to infection and differences in tuberculosis (TB) disease outcome. Toll-like receptor 9 (TLR9) is a pattern recognition receptor that mediates recognition of Mtb and modulates Mtb-specific T-cell responses. Using a case-population design, we evaluated whether single nucleotide polymorphisms (SNPs) in the TLR9 gene region are associated with susceptibility to pulmonary or meningeal TB as well as neurologic presentation and mortality in the meningeal TB group. In a discovery cohort (n = 352 cases, 382 controls), three SNPs were associated with TB (all forms, p < 0.05) while three additional SNPs neared significance (0.05 < p < 0.1). When these six SNPs were evaluated in a validation cohort (n = 339 cases, 367 controls), one was significant (rs352142) while another neared significance (rs352143). When the cohorts were combined, rs352142 was most strongly associated with meningeal tuberculosis (dominant model; p = 0.0002, OR 2.36, CI 1.43-3.87) while rs352143 was associated with pulmonary tuberculosis (recessive model; p = 0.006, OR 5.3, CI 1.26-31.13). None of the SNPs were associated with mortality. This is the first demonstration of an association between a TLR9 gene region SNP and tuberculous meningitis. In addition, this extends previous findings that support associations of TLR9 SNPs with pulmonary tuberculosis.
authors.affiliation: Univ. of Washington, Seattle, WA, USA. Electronic address: adg2001@u.washington.edu.
authors.forename: A D
authors.initials: AD
authors.lastname: Graustein
authors.affiliation: Univ. of Washington, Seattle, WA, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Horne
authors.affiliation: Univ. of Washington, Seattle, WA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Arentz
authors.affiliation: Pham Ngoc Thach Hospital for Tuberculosis & Lung Disease, HCMC, Viet Nam.
authors.forename: N D
authors.initials: ND
authors.lastname: Bang
authors.affiliation: Hospital for Tropical Diseases, HCMC, Viet Nam.
authors.forename: T T H
authors.initials: TT
authors.lastname: Chau
authors.affiliation: Oxford Univ. Clinical Research Unit, Hospital for Tropical Diseases, HCMC, Viet Nam; Nuffield Dept. of Clinical Medicine, Centre for Tropical Medicine, Oxford Univ., UK.
authors.forename: G E
authors.initials: GE
authors.lastname: Thwaites
authors.affiliation: Oxford Univ. Clinical Research Unit, Hospital for Tropical Diseases, HCMC, Viet Nam; Liverpool School of Tropical Medicine, Pembroke Place, UK.
authors.forename: M
authors.initials: M
authors.lastname: Caws
authors.affiliation: Oxford Univ. Clinical Research Unit, Hospital for Tropical Diseases, HCMC, Viet Nam; Nuffield Dept. of Clinical Medicine, Centre for Tropical Medicine, Oxford Univ., UK.
authors.forename: N T T
authors.initials: NT
authors.lastname: Thuong
authors.affiliation: Oxford Univ. Clinical Research Unit, Hospital for Tropical Diseases, HCMC, Viet Nam; Nuffield Dept. of Clinical Medicine, Centre for Tropical Medicine, Oxford Univ., UK; The Nossal Institute for Global Health, The University of Melbourne, Australia.
authors.forename: S J
authors.initials: SJ
authors.lastname: Dunstan
authors.affiliation: Univ. of Washington, Seattle, WA, USA.
authors.forename: T R
authors.initials: TR
authors.lastname: Hawn
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D051217:Toll-Like Receptor 9 / Q000235:genetics*; D014376:Tuberculosis / Q000453:epidemiology / Q000235:genetics*; D014390:Tuberculosis, Meningeal / Q000453:epidemiology / Q000235:genetics; D014397:Tuberculosis, Pulmonary / Q000453:epidemiology / Q000235:genetics; D014744:Vietnam / Q000453:epidemiology; D055815:Young Adult
chemical_list: C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9
keywords: Meningitis; Mycobacterium tuberculosis; TLR9; Tuberculosis