A SNP upstream of the cyclic GMP-AMP synthase (cGAS) gene protects from relapse and extra-pulmonary TB and relates to BCG vaccination status in an Indian cohort.

Autor: Thada S; Institute for Microbiology and Hygiene, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.; Bhagwan Mahavir Medical Research Centre, Hyderabad, India., Burkert S; Institute for Microbiology and Hygiene, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany., Sivangala R; Bhagwan Mahavir Medical Research Centre, Hyderabad, India., Hussain A; Department of Biotechnology and Bioinformatics, University of Hyderabad, Hyderabad, India., Sur S; Institute for Microbiology and Hygiene, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany., Dittrich N; Institute for Microbiology and Hygiene, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany., Conrad ML; Institute for Microbiology and Hygiene, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.; Division of Psychosomatic Medicine, Department of Internal Medicine and Dermatology, Charite-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany., Slevogt H; Institute for Microbiology and Hygiene, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.; ZIK Septomics, Jena University Hospital, Jena, Germany., Latha Gaddam S; Bhagwan Mahavir Medical Research Centre, Hyderabad, India.; Department of Genetics, Osmania University, Hyderabad, India., Schumann RR; Institute for Microbiology and Hygiene, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany. ralf.schumann@charite.de.
Jazyk: angličtina
Zdroj: Genes and immunity [Genes Immun] 2020 Jan; Vol. 21 (1), pp. 13-26. Date of Electronic Publication: 2019 May 23.
DOI: 10.1038/s41435-019-0080-1
Abstrakt: Tuberculosis (TB) caused by Mycobacterium tuberculosis (M.tb) is a major health care threat worldwide causing over a million deaths annually. Host-pathogen interaction is complex, and a strong genetic contribution to disease susceptibility has been proposed. We have investigated single-nucleotide polymorphisms (SNPs) within cGAS/STING in Indian TB patients and healthy cohorts from India and Germany by Lightcycler®480 genotyping technique. The cGAS/STING pathway is an essential defense pathway within the cytosol after M.tb is internalized and mycobacterial DNA is released inducing the production of type I IFNs. We found that the rs311686 SNP upstream of cGAS provides protection from getting TB overall and is differently distributed in pulmonary TB patients compared with extra-pulmonary and particularly relapse cases. This SNP furthermore differs in distribution when comparing individuals with respect to BCG vaccination status. Taken together, our results show that the presence of the rs311686 SNP influences the course of TB significantly. However, structural conformation changes were found only for the cGAS rs610913 SNP. These findings underscore the importance of M.tb DNA recognition for TB pathogenesis and may eventually help in risk stratification of individuals. This may ultimately help in prevention of disease and aid in developing new vaccination and treatment strategies.
Databáze: MEDLINE
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