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 - Funding Information:
This project has been funded wholly or in part by Federal funds from the Government of India's (GOI’) Department of Biotechnology (DBT, New Delhi), the Indian Council of Medical Research (ICMR, New Delhi, India), the United States National Institutes of Health (NIH, Bethesda, MD), National Institute of Allergy and Infectious Diseases (NIAID; Bethesda, MD), Office of AIDS Research (OAR; Bethesda, MD), and distributed in part by Civilian Research Development Foundation (CRDF) Global (Arlington, VA, USA). We would like to acknowledge all the members of the CTRIUMPH study team listed in alphabetical order - Aarti Kinikar, Amita Nagraj, Anand Kumar B, Andrea DeLuca, Anita More, Anju Kagal, Archana Gaikwad, Ashwini Nangude, Balaji S, Beena Thomas, Bency Joseph, Bharath TK, Brindha B, Chandrasekaran P, David Dowdy, Deepak Pole, Devanathan A, Devi Sangamithrai M, Dileep Kadam, Divyashri Jain, Dolla CK, Gabriela Smit, Gangadarsharma R, Geetha Ramachandran, Hanumant Chaugule, Hari Koli, Hemanth kumar, Jeeva J, Jessica Elf, Jonathan Golub, Jyoti Chandane, Kanade Savita, Karthikesh M, Karunakaran S, Kelly Dooley, Krithiiga Sekar, Lakshmi Murali, Lavanya M, Madasamy S, Mageshkumar M, Mangaiyarkarasi S, Mahesh Gujare, Manoharan S, Michel Premkumar M, Munivardhan P, Nagaraj, Nishi Suryavanshi, Ponnuraja C, Premkumar N, Rahul Lokhande, Rajkumar S, Ranganathan K, Rani S, Rani V, Renu Bharadwaj, Renu Madewar, Rengaraj R, Rewa Kohli, Rosemarie Warlick, Rupak Shivakoti, Sahadev Javanjal, Sameer Joshi, Sandhya Khadse, Shalini Pawar, Shashank Hande, Shital Muley, Shital Sali, Suba priya K, Shrinivas B.M., Shyam Biswal, Silambu Chelvi K, Smita Nimkar, Soumya Swaminathan, Sriram Selvaraj, Sundeep Salvi, Sushant Meshram, Surendhar S, Swapnil Raskar, Uma Devi, Vidula Hulyalkar, Vinod Tayawade, Vrinda Bansode, Yogesh Daware.
Funding Information:
This project has been funded wholly or in part by Federal funds from the Government of India's (GOI?) Department of Biotechnology (DBT, New Delhi), the Indian Council of Medical Research (ICMR, New Delhi, India), the United States National Institutes of Health (NIH, Bethesda, MD), National Institute of Allergy and Infectious Diseases (NIAID; Bethesda, MD), Office of AIDS Research (OAR; Bethesda, MD), and distributed in part by Civilian Research Development Foundation (CRDF) Global (Arlington, VA, USA). We would like to acknowledge all the members of the CTRIUMPH study team listed in alphabetical order - Aarti Kinikar, Amita Nagraj, Anand Kumar B, Andrea DeLuca, Anita More, Anju Kagal, Archana Gaikwad, Ashwini Nangude, Balaji S, Beena Thomas, Bency Joseph, Bharath TK, Brindha B, Chandrasekaran P, David Dowdy, Deepak Pole, Devanathan A, Devi Sangamithrai M, Dileep Kadam, Divyashri Jain, Dolla CK, Gabriela Smit, Gangadarsharma R, Geetha Ramachandran, Hanumant Chaugule, Hari Koli, Hemanth kumar, Jeeva J, Jessica Elf, Jonathan Golub, Jyoti Chandane, Kanade Savita, Karthikesh M, Karunakaran S, Kelly Dooley, Krithiiga Sekar, Lakshmi Murali, Lavanya M, Madasamy S, Mageshkumar M, Mangaiyarkarasi S, Mahesh Gujare, Manoharan S, Michel Premkumar M, Munivardhan P, Nagaraj, Nishi Suryavanshi, Ponnuraja C, Premkumar N, Rahul Lokhande, Rajkumar S, Ranganathan K, Rani S, Rani V, Renu Bharadwaj, Renu Madewar, Rengaraj R, Rewa Kohli, Rosemarie Warlick, Rupak Shivakoti, Sahadev Javanjal, Sameer Joshi, Sandhya Khadse, Shalini Pawar, Shashank Hande, Shital Muley, Shital Sali, Suba priya K, Shrinivas B.M. Shyam Biswal, Silambu Chelvi K, Smita Nimkar, Soumya Swaminathan, Sriram Selvaraj, Sundeep Salvi, Sushant Meshram, Surendhar S, Swapnil Raskar, Uma Devi, Vidula Hulyalkar, Vinod Tayawade, Vrinda Bansode, Yogesh Daware.
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
UR - http://www.scopus.com/inward/record.url?scp=85074780911&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85074780911&partnerID=8YFLogxK
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 -