TY - JOUR
T1 - MAL adaptor (TIRAP) S180L polymorphism and severity of disease among tuberculosis patients
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
N1 - Publisher Copyright:
© 2019 Elsevier B.V.
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.
KW - IP-10
KW - Interferon-gamma
KW - Mal adaptor
KW - S180L variant
KW - TIRAP
KW - Tuberculosis
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U2 - 10.1016/j.meegid.2019.104093
DO - 10.1016/j.meegid.2019.104093
M3 - Article
C2 - 31678649
AN - SCOPUS:85074780911
SN - 1567-1348
VL - 77
JO - Infection, Genetics and Evolution
JF - Infection, Genetics and Evolution
M1 - 104093
ER -