Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pgen.1000218
Title: Genetic association and expression studies indicate a role of Toll-like receptor 8 in pulmonary tuberculosis
Authors: Davila S.
Hibberd M.L. 
Dass R.H.
Wong H.E.E.
Sahiratmadja E.
Bonnard C.
Alisjahbana B.
Szeszko J.S.
Balabanova Y.
Drobniewski F.
Van Crevel R.
Van De Vosse E.
Nejentsev S.
Ottenhoff T.H.M.
Seielstad M.
Keywords: toll like receptor 8
messenger RNA
TLR8 protein, human
adolescent
adult
aged
article
controlled study
DNA polymorphism
female
gene expression
gene sequence
genetic analysis
genetic susceptibility
human
lung tuberculosis
major clinical study
male
Mycobacterium tuberculosis
nucleotide sequence
polymerase chain reaction
single nucleotide polymorphism
X chromosome
case control study
cell line
gene frequency
gene linkage disequilibrium
genetic predisposition
genetics
haplotype
immunology
Indonesia
metabolism
middle aged
sexual development
Mycobacterium tuberculosis
Adolescent
Adult
Aged
Aged, 80 and over
Case-Control Studies
Cell Line
Chromosomes, Human, X
Female
Gene Expression
Gene Frequency
Genetic Predisposition to Disease
Haplotypes
Humans
Indonesia
Linkage Disequilibrium
Male
Middle Aged
Polymorphism, Single Nucleotide
RNA, Messenger
Sex Characteristics
Toll-Like Receptor 8
Tuberculosis, Pulmonary
Issue Date: 2008
Citation: Davila S., Hibberd M.L., Dass R.H., Wong H.E.E., Sahiratmadja E., Bonnard C., Alisjahbana B., Szeszko J.S., Balabanova Y., Drobniewski F., Van Crevel R., Van De Vosse E., Nejentsev S., Ottenhoff T.H.M., Seielstad M. (2008). Genetic association and expression studies indicate a role of Toll-like receptor 8 in pulmonary tuberculosis. PLoS Genetics 4 (10) : e1000218. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pgen.1000218
Abstract: Despite high rates of exposure, only 5-10% of people infected with Mycobacterium tuberculosis will develop active tuberculosis (TB) disease, suggesting a significant role for genetic variation in the human immune response to this infection. Here, we studied TB association and expression of 18 genes involved in the Toll-like receptor (TLR) pathways. Initially, we genotyped 149 sequence polymorphisms in 375 pulmonary TB patients and 387 controls from Indonesia. We found that four polymorphisms in the TLR8 gene on chromosome X showed evidence of association with TB susceptibility in males, including a non-synonymous polymorphism rs3764880 (Met1Val; P = 0.007, odds ratio (OR) = 1.8, 95% c.i. = 1.2-2.7). We genotyped these four TLR8 polymorphisms in an independent collection of 1,837 pulmonary TB patients and 1,779 controls from Russia and again found evidence of association in males (for rs3764880 P = 0.03, OR = 1.2, 95% c.i. = 1.02-1.48). Combined evidence for association is P = 1.2×10-3-6×10-4. In addition, a quantitative PCR analysis indicated that TLR8 transcript levels are significantly up-regulated in patients during the acute phase of disease (P = 9.3661025), relative to baseline levels following successful chemotherapy. A marked increase in TLR8 protein expression was also observed directly in differentiated macrophages upon infection with M. bovis bacille Calmette-Guérin (BCG). Taken together, our results provide evidence, for the first time, of a role for the TLR8 gene in susceptibility to pulmonary TB across different populations. © 2008 Davila et al.
Source Title: PLoS Genetics
URI: https://scholarbank.nus.edu.sg/handle/10635/161682
ISSN: 15537390
DOI: 10.1371/journal.pgen.1000218
Appears in Collections:Elements
Staff Publications

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_1371_journal_pgen_1000218.pdf241.83 kBAdobe PDF

OPEN

NoneView/Download

SCOPUSTM   
Citations

182
checked on Oct 15, 2020

Page view(s)

83
checked on Oct 16, 2020

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.