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.
Shruthi ThadaSanne BurkertRamya SivangalaAbid HussainSaubashya SurNickel DittrichMelanie L ConradHortense SlevogtSuman Latha GaddamRalf R SchumannPublished in: Genes and immunity (2019)
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.
Keyphrases
- mycobacterium tuberculosis
- genome wide
- pulmonary tuberculosis
- healthcare
- end stage renal disease
- newly diagnosed
- pulmonary hypertension
- dna methylation
- ejection fraction
- copy number
- genetic diversity
- high density
- circulating tumor
- transcription factor
- escherichia coli
- single molecule
- candida albicans
- electronic health record
- crystal structure
- adverse drug
- drug induced
- biofilm formation