MAL adaptor (TIRAP) S180L polymorphism and severity of disease among tuberculosis patients

for the C-TRIUMPh Study Team

Research output: Contribution to journalArticle

Abstract

Objective: Though several genetic variants have been recognized to be associated with susceptibility to Tuberculosis (TB) infection and disease, a recent observation on the association of TIRAP C975T (S180L) variants with TB disease severity in mice model prompted us to assess their relevance in humans. In addition, TIRAP variants have also been reported to be associated with varied circulating Interferon-gamma induced protein (IP-10) levels. We investigated the association of TIRAP variants with severity of TB disease and IP-10 production in humans, which may be useful in predicting poor clinical outcome. Methods: Culture positive symptomatic adult pulmonary TB (PTB) patients enrolled between August 2014 and October 2017 were included in this investigation. Allelic discrimination PCR and conventional IP-10 quantification methods were employed for genotyping and IP-10 measurement followed by statistical investigations to analyse patients' variables. Results: Among 211 participants, C/C allele was identified in 70% (n = 147); 26% (n = 55) and 4% (n = 9) had C/T and T/T alleles respectively. There was no significant association between TIRAP variants and smear grade, chest-X-ray score, symptom severity score and circulating IP-10 levels. However, significant association was observed between i) circulating IP-10 levels and time to Mycobacterium Growth Indicator Tube (MGIT) culture conversion (p =0.032); ii) smear grade among active TB patients and circulating IP-10 levels (p =0.032). Conclusions: Although mice experiments showed promising results with more severe disease in C/C and T/T individuals, we did not observe any such association in humans.

Original languageEnglish (US)
Article number104093
JournalInfection, Genetics and Evolution
Volume77
DOIs
StatePublished - Jan 2020

Fingerprint

tuberculosis
disease severity
Tuberculosis
polymorphism
genetic polymorphism
Alleles
allele
alleles
Mycobacterium
Pulmonary Tuberculosis
Interferon-gamma
chest
interferon-gamma
Thorax
genotyping
signs and symptoms (animals and humans)
X-Rays
X-radiation
Polymerase Chain Reaction
animal models

Keywords

  • Interferon-gamma
  • IP-10
  • Mal adaptor
  • S180L variant
  • TIRAP
  • Tuberculosis

ASJC Scopus subject areas

  • Microbiology
  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Microbiology (medical)
  • Infectious Diseases

Cite this

MAL adaptor (TIRAP) S180L polymorphism and severity of disease among tuberculosis patients. / for the C-TRIUMPh Study Team.

In: Infection, Genetics and Evolution, Vol. 77, 104093, 01.2020.

Research output: Contribution to journalArticle

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title = "MAL adaptor (TIRAP) S180L polymorphism and severity of disease among tuberculosis patients",
abstract = "Objective: Though several genetic variants have been recognized to be associated with susceptibility to Tuberculosis (TB) infection and disease, a recent observation on the association of TIRAP C975T (S180L) variants with TB disease severity in mice model prompted us to assess their relevance in humans. In addition, TIRAP variants have also been reported to be associated with varied circulating Interferon-gamma induced protein (IP-10) levels. We investigated the association of TIRAP variants with severity of TB disease and IP-10 production in humans, which may be useful in predicting poor clinical outcome. Methods: Culture positive symptomatic adult pulmonary TB (PTB) patients enrolled between August 2014 and October 2017 were included in this investigation. Allelic discrimination PCR and conventional IP-10 quantification methods were employed for genotyping and IP-10 measurement followed by statistical investigations to analyse patients' variables. Results: Among 211 participants, C/C allele was identified in 70{\%} (n = 147); 26{\%} (n = 55) and 4{\%} (n = 9) had C/T and T/T alleles respectively. There was no significant association between TIRAP variants and smear grade, chest-X-ray score, symptom severity score and circulating IP-10 levels. However, significant association was observed between i) circulating IP-10 levels and time to Mycobacterium Growth Indicator Tube (MGIT) culture conversion (p =0.032); ii) smear grade among active TB patients and circulating IP-10 levels (p =0.032). Conclusions: Although mice experiments showed promising results with more severe disease in C/C and T/T individuals, we did not observe any such association in humans.",
keywords = "Interferon-gamma, IP-10, Mal adaptor, S180L variant, TIRAP, Tuberculosis",
author = "{for the C-TRIUMPh Study Team} and Rajagopalan Saranathan and Pattabiraman Sathyamurthi and Kannan Thiruvengadam and Selvachithiram Murugesan and Shivakumar, {Shri Vijay Bala Yogendra} and Gomathi, {Narayanan Sivaramakrishnan} and Dhanasekaran Kavitha and Mandar Paradkar and Rohini Puvaneshwari and Muthuramalingam Kannan and Annamalai Madheswaran and Neeta Pradhan and Vandana Kulkarni and Gupte, {Akshay N.} and Nikhil Gupte and Vidya Mave and Bollinger, {Robert C.} and Amita Gupta and Chandrasekaran Padmapriyadarsini and Hanna, {Luke Elizabeth}",
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AU - for the C-TRIUMPh Study Team

AU - Saranathan, Rajagopalan

AU - Sathyamurthi, Pattabiraman

AU - Thiruvengadam, Kannan

AU - Murugesan, Selvachithiram

AU - Shivakumar, Shri Vijay Bala Yogendra

AU - Gomathi, Narayanan Sivaramakrishnan

AU - Kavitha, Dhanasekaran

AU - Paradkar, Mandar

AU - Puvaneshwari, Rohini

AU - Kannan, Muthuramalingam

AU - Madheswaran, Annamalai

AU - Pradhan, Neeta

AU - Kulkarni, Vandana

AU - Gupte, Akshay N.

AU - Gupte, Nikhil

AU - Mave, Vidya

AU - Bollinger, Robert C.

AU - Gupta, Amita

AU - Padmapriyadarsini, Chandrasekaran

AU - Hanna, Luke Elizabeth

PY - 2020/1

Y1 - 2020/1

N2 - Objective: Though several genetic variants have been recognized to be associated with susceptibility to Tuberculosis (TB) infection and disease, a recent observation on the association of TIRAP C975T (S180L) variants with TB disease severity in mice model prompted us to assess their relevance in humans. In addition, TIRAP variants have also been reported to be associated with varied circulating Interferon-gamma induced protein (IP-10) levels. We investigated the association of TIRAP variants with severity of TB disease and IP-10 production in humans, which may be useful in predicting poor clinical outcome. Methods: Culture positive symptomatic adult pulmonary TB (PTB) patients enrolled between August 2014 and October 2017 were included in this investigation. Allelic discrimination PCR and conventional IP-10 quantification methods were employed for genotyping and IP-10 measurement followed by statistical investigations to analyse patients' variables. Results: Among 211 participants, C/C allele was identified in 70% (n = 147); 26% (n = 55) and 4% (n = 9) had C/T and T/T alleles respectively. There was no significant association between TIRAP variants and smear grade, chest-X-ray score, symptom severity score and circulating IP-10 levels. However, significant association was observed between i) circulating IP-10 levels and time to Mycobacterium Growth Indicator Tube (MGIT) culture conversion (p =0.032); ii) smear grade among active TB patients and circulating IP-10 levels (p =0.032). Conclusions: Although mice experiments showed promising results with more severe disease in C/C and T/T individuals, we did not observe any such association in humans.

AB - Objective: Though several genetic variants have been recognized to be associated with susceptibility to Tuberculosis (TB) infection and disease, a recent observation on the association of TIRAP C975T (S180L) variants with TB disease severity in mice model prompted us to assess their relevance in humans. In addition, TIRAP variants have also been reported to be associated with varied circulating Interferon-gamma induced protein (IP-10) levels. We investigated the association of TIRAP variants with severity of TB disease and IP-10 production in humans, which may be useful in predicting poor clinical outcome. Methods: Culture positive symptomatic adult pulmonary TB (PTB) patients enrolled between August 2014 and October 2017 were included in this investigation. Allelic discrimination PCR and conventional IP-10 quantification methods were employed for genotyping and IP-10 measurement followed by statistical investigations to analyse patients' variables. Results: Among 211 participants, C/C allele was identified in 70% (n = 147); 26% (n = 55) and 4% (n = 9) had C/T and T/T alleles respectively. There was no significant association between TIRAP variants and smear grade, chest-X-ray score, symptom severity score and circulating IP-10 levels. However, significant association was observed between i) circulating IP-10 levels and time to Mycobacterium Growth Indicator Tube (MGIT) culture conversion (p =0.032); ii) smear grade among active TB patients and circulating IP-10 levels (p =0.032). Conclusions: Although mice experiments showed promising results with more severe disease in C/C and T/T individuals, we did not observe any such association in humans.

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KW - TIRAP

KW - Tuberculosis

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