Publication: Common TLR1 genetic variation is not associated with death from melioidosis, a common cause of sepsis in rural Thailand
Accepted Date
2013-11-12
Issued Date
2014-01-02
Copyright Date
2014
Resource Type
Language
eng
ISSN
1932-6203 (electronic)
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Mahidol University
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PLoS ONE
Bibliographic Citation
Chantratita N, Tandhavanant S, Myers ND, Chierakul W, Wuthiekanun V, Mahavanakul W, et al. Common TLR1 genetic variation is not associated with death from melioidosis, a common cause of sepsis in rural Thailand. PLoS One. 2014 Jan 2;9(1):e83285.
Suggested Citation
Narisara Chantratita, นริศรา จันทราทิตย์, Sarunporn Tandhavanant, ศรัณย์พร ตัณฑวนันท์, Myers, Nicolle D., Wirongrong Chierakul, วิรงค์รอง เจียรกุล, Vanaporn Wuthiekanun, วรรณพร วุฒิเอกอนันต์, Weera Mahavanakul, Direk Limmathurotsakul, ดิเรก ลิ้มมธุรสกุล, Peacock, Sharon J., West, T. Eoin Common TLR1 genetic variation is not associated with death from melioidosis, a common cause of sepsis in rural Thailand. Chantratita N, Tandhavanant S, Myers ND, Chierakul W, Wuthiekanun V, Mahavanakul W, et al. Common TLR1 genetic variation is not associated with death from melioidosis, a common cause of sepsis in rural Thailand. PLoS One. 2014 Jan 2;9(1):e83285.. doi:10.1371/journal.pone.0083285 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/660
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Title
Common TLR1 genetic variation is not associated with death from melioidosis, a common cause of sepsis in rural Thailand
Corresponding Author(s)
Other Contributor(s)
Mahidol University. Faculty of Tropical Medicine. Department of Microbiology and Immunology
Mahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Tropical Medicine Research Unit
Mahidol University. Faculty of Tropical Medicine. Department of Clinical Tropical Medicine
Mahidol University. Faculty of Tropical Medicine. Department of Tropical Hygiene
Mahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Tropical Medicine Research Unit
Mahidol University. Faculty of Tropical Medicine. Department of Clinical Tropical Medicine
Mahidol University. Faculty of Tropical Medicine. Department of Tropical Hygiene
Abstract
Melioidosis, infection caused by the Gram-negative bacterium Burkholderia
pseudomallei, is a common cause of sepsis in northeast Thailand. In white North
Americans, common functional genetic variation in TLR1 is associated with organ
failure and death from sepsis. We hypothesized that TLR1 variants would be
associated with outcomes in Thais with melioidosis. We collated the global
frequencies of three TLR1 variants that are common in white North American
populations: rs5743551 (-7202A/G), rs4833095 (742A/G), and rs5743618 (1804G/T).
We noted a reversal of the minor allele from white North American subjects to
Asian populations that was particularly pronounced for rs5743618. In the Utah
residents of European ancestry, the frequency of the rs5743618 T allele was 17%
whereas in Vietnamese subjects the frequency was >99%. We conducted a genetic
association study in 427 patients with melioidosis to determine the association
of TLR1 variation with organ failure or death. We genotyped rs5743551 and
rs4833095. The variants were in high linkage disequilibrium but neither variant
was associated with organ failure or in-hospital death. In 300 healthy Thai
individuals we further tested the association of TLR1 variation with ex vivo
blood responses to Pam3CSK4, a TLR1 agonist. Neither variant was robustly
associated with blood cytokine responses induced by Pam3CSK4. We identified
additional common variation in TLR1 by searching public databases and the
published literature and screened three additional TLR1 variants for associations
with Pam3CSK4-induced responses but found none. We conclude that the genetic
architecture of TLR1 variation differs substantially in southeast Asians compared
to other populations and common variation in TLR1 in Thais is not associated with
outcome from melioidosis or with altered blood responses to Pam3CSK4. Our
findings highlight the need for additional studies of TLR1 and other innate
immune genetic modulators of the inflammatory host response and determinants of
sepsis in southeast Asian populations.