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
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...
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| Veröffentlicht in: | Genes and immunity 2020-01, Vol.21 (1), p.13-26 |
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| creator | Thada, Shruthi Burkert, Sanne Sivangala, Ramya Hussain, Abid Sur, Saubashya Dittrich, Nickel Conrad, Melanie L. Slevogt, Hortense Latha Gaddam, Suman Schumann, Ralf R. |
| description | 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. |
| doi_str_mv | 10.1038/s41435-019-0080-1 |
| format | Article |
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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.</description><identifier>ISSN: 1466-4879</identifier><identifier>EISSN: 1476-5470</identifier><identifier>DOI: 10.1038/s41435-019-0080-1</identifier><identifier>PMID: 31118495</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>45 ; 45/22 ; 45/43 ; 45/77 ; 631/208/457 ; 631/250/255/1856 ; Adult ; AMP ; Bacillus Calmette-Guerin vaccine ; BCG ; BCG Vaccine - administration & dosage ; BCG Vaccine - immunology ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Case-Control Studies ; Cohort Studies ; Conformation ; Cyclic GMP ; Cytosol ; Deoxyribonucleic acid ; DNA ; Female ; Gene Expression ; Genetic aspects ; Genotyping ; Health aspects ; Host-Pathogen Interactions ; Human Genetics ; Human immunogenetics ; Humans ; Immunization ; Immunology ; India - epidemiology ; Male ; Mycobacterium tuberculosis - genetics ; Nucleotidyltransferases - genetics ; Nucleotidyltransferases - metabolism ; Patients ; Polymorphism, Single Nucleotide ; Recurrence ; Signal Transduction ; Single nucleotide polymorphisms ; Single-nucleotide polymorphism ; Tuberculosis ; Tuberculosis - enzymology ; Tuberculosis - genetics ; Tuberculosis - immunology ; Tuberculosis - microbiology ; Vaccination</subject><ispartof>Genes and immunity, 2020-01, Vol.21 (1), p.13-26</ispartof><rights>Springer Nature Limited 2019</rights><rights>COPYRIGHT 2020 Nature Publishing Group</rights><rights>Springer Nature Limited 2019.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c439t-1a5860a6b6c3cc30cc08a589bc30fa09918e20ce2f7f9bba37d82b3b8ae6ccba3</citedby><cites>FETCH-LOGICAL-c439t-1a5860a6b6c3cc30cc08a589bc30fa09918e20ce2f7f9bba37d82b3b8ae6ccba3</cites><orcidid>0000-0001-7002-628X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s41435-019-0080-1$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41435-019-0080-1$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27903,27904,41467,42536,51297</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31118495$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Thada, Shruthi</creatorcontrib><creatorcontrib>Burkert, Sanne</creatorcontrib><creatorcontrib>Sivangala, Ramya</creatorcontrib><creatorcontrib>Hussain, Abid</creatorcontrib><creatorcontrib>Sur, Saubashya</creatorcontrib><creatorcontrib>Dittrich, Nickel</creatorcontrib><creatorcontrib>Conrad, Melanie L.</creatorcontrib><creatorcontrib>Slevogt, Hortense</creatorcontrib><creatorcontrib>Latha Gaddam, Suman</creatorcontrib><creatorcontrib>Schumann, Ralf R.</creatorcontrib><title>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</title><title>Genes and immunity</title><addtitle>Genes Immun</addtitle><addtitle>Genes Immun</addtitle><description>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.</description><subject>45</subject><subject>45/22</subject><subject>45/43</subject><subject>45/77</subject><subject>631/208/457</subject><subject>631/250/255/1856</subject><subject>Adult</subject><subject>AMP</subject><subject>Bacillus Calmette-Guerin vaccine</subject><subject>BCG</subject><subject>BCG Vaccine - administration & dosage</subject><subject>BCG Vaccine - immunology</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Case-Control Studies</subject><subject>Cohort Studies</subject><subject>Conformation</subject><subject>Cyclic GMP</subject><subject>Cytosol</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Female</subject><subject>Gene Expression</subject><subject>Genetic aspects</subject><subject>Genotyping</subject><subject>Health aspects</subject><subject>Host-Pathogen Interactions</subject><subject>Human Genetics</subject><subject>Human immunogenetics</subject><subject>Humans</subject><subject>Immunization</subject><subject>Immunology</subject><subject>India - epidemiology</subject><subject>Male</subject><subject>Mycobacterium tuberculosis - genetics</subject><subject>Nucleotidyltransferases - genetics</subject><subject>Nucleotidyltransferases - metabolism</subject><subject>Patients</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Recurrence</subject><subject>Signal Transduction</subject><subject>Single nucleotide polymorphisms</subject><subject>Single-nucleotide polymorphism</subject><subject>Tuberculosis</subject><subject>Tuberculosis - enzymology</subject><subject>Tuberculosis - genetics</subject><subject>Tuberculosis - immunology</subject><subject>Tuberculosis - microbiology</subject><subject>Vaccination</subject><issn>1466-4879</issn><issn>1476-5470</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1kk1v1DAQhiMEoh_wA7ggS1zKIcUfieMctytYKrWwUsvZciaT3VSJvdgOYv8NP7UOW6hAIB_GHj_vaGb0ZtkrRs8ZFepdKFghypyyOqdU0Zw9yY5ZUcm8LCr6dL5LmReqqo-ykxDuKGWSyfp5diQYY6qoy-Psx4LcfFqTaReiRzMS15G4RQJ7GHogq-t1vrhek7C3cWsCkjNYLW7ekg1aJDvvIkIMpPNuJB4Hs0uEsS3B79GbfDcNo7PG78ntxc_0jEQMJDpysVyRbwagtyb2zpIQTZwC6W0CyaVt-xTAbZ2PL7JnnRkCvnyIp9mXD-9vlx_zq8-ry-XiKodC1DFnplSSGtlIEACCAlCVUnWT7p2hdc0UcgrIu6qrm8aIqlW8EY0yKAHS-zQ7O9RNY32dMEQ99gFwGIxFNwXNueCM8krxhL75C71zk7epO82FFJRyVYhHamMG1L3tXFoKzEX1QjLFS8XKmTr_B5VOi2MPzmLXp_wfAnYQgHcheOz0zvdj2rJmVM-u0AdX6OQKPbtCs6R5_dDw1IzY_lb8skEC-AEI6ctu0D9O9P-q90aRwJw</recordid><startdate>20200101</startdate><enddate>20200101</enddate><creator>Thada, Shruthi</creator><creator>Burkert, Sanne</creator><creator>Sivangala, Ramya</creator><creator>Hussain, Abid</creator><creator>Sur, Saubashya</creator><creator>Dittrich, Nickel</creator><creator>Conrad, Melanie L.</creator><creator>Slevogt, Hortense</creator><creator>Latha Gaddam, Suman</creator><creator>Schumann, Ralf R.</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-7002-628X</orcidid></search><sort><creationdate>20200101</creationdate><title>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</title><author>Thada, Shruthi ; Burkert, Sanne ; Sivangala, Ramya ; Hussain, Abid ; Sur, Saubashya ; Dittrich, Nickel ; Conrad, Melanie L. ; Slevogt, Hortense ; Latha Gaddam, Suman ; Schumann, Ralf R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c439t-1a5860a6b6c3cc30cc08a589bc30fa09918e20ce2f7f9bba37d82b3b8ae6ccba3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>45</topic><topic>45/22</topic><topic>45/43</topic><topic>45/77</topic><topic>631/208/457</topic><topic>631/250/255/1856</topic><topic>Adult</topic><topic>AMP</topic><topic>Bacillus Calmette-Guerin vaccine</topic><topic>BCG</topic><topic>BCG Vaccine - administration & dosage</topic><topic>BCG Vaccine - immunology</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Case-Control Studies</topic><topic>Cohort Studies</topic><topic>Conformation</topic><topic>Cyclic GMP</topic><topic>Cytosol</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>Female</topic><topic>Gene Expression</topic><topic>Genetic aspects</topic><topic>Genotyping</topic><topic>Health aspects</topic><topic>Host-Pathogen Interactions</topic><topic>Human Genetics</topic><topic>Human immunogenetics</topic><topic>Humans</topic><topic>Immunization</topic><topic>Immunology</topic><topic>India - epidemiology</topic><topic>Male</topic><topic>Mycobacterium tuberculosis - genetics</topic><topic>Nucleotidyltransferases - genetics</topic><topic>Nucleotidyltransferases - metabolism</topic><topic>Patients</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Recurrence</topic><topic>Signal Transduction</topic><topic>Single nucleotide polymorphisms</topic><topic>Single-nucleotide polymorphism</topic><topic>Tuberculosis</topic><topic>Tuberculosis - enzymology</topic><topic>Tuberculosis - genetics</topic><topic>Tuberculosis - immunology</topic><topic>Tuberculosis - microbiology</topic><topic>Vaccination</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Thada, Shruthi</creatorcontrib><creatorcontrib>Burkert, Sanne</creatorcontrib><creatorcontrib>Sivangala, Ramya</creatorcontrib><creatorcontrib>Hussain, Abid</creatorcontrib><creatorcontrib>Sur, Saubashya</creatorcontrib><creatorcontrib>Dittrich, Nickel</creatorcontrib><creatorcontrib>Conrad, Melanie L.</creatorcontrib><creatorcontrib>Slevogt, Hortense</creatorcontrib><creatorcontrib>Latha Gaddam, Suman</creatorcontrib><creatorcontrib>Schumann, Ralf R.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Genes and immunity</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Thada, Shruthi</au><au>Burkert, Sanne</au><au>Sivangala, Ramya</au><au>Hussain, Abid</au><au>Sur, Saubashya</au><au>Dittrich, Nickel</au><au>Conrad, Melanie L.</au><au>Slevogt, Hortense</au><au>Latha Gaddam, Suman</au><au>Schumann, Ralf R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>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</atitle><jtitle>Genes and immunity</jtitle><stitle>Genes Immun</stitle><addtitle>Genes Immun</addtitle><date>2020-01-01</date><risdate>2020</risdate><volume>21</volume><issue>1</issue><spage>13</spage><epage>26</epage><pages>13-26</pages><issn>1466-4879</issn><eissn>1476-5470</eissn><abstract>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.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>31118495</pmid><doi>10.1038/s41435-019-0080-1</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0001-7002-628X</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1466-4879 |
| ispartof | Genes and immunity, 2020-01, Vol.21 (1), p.13-26 |
| issn | 1466-4879 1476-5470 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2232102782 |
| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | 45 45/22 45/43 45/77 631/208/457 631/250/255/1856 Adult AMP Bacillus Calmette-Guerin vaccine BCG BCG Vaccine - administration & dosage BCG Vaccine - immunology Biomedical and Life Sciences Biomedicine Cancer Research Case-Control Studies Cohort Studies Conformation Cyclic GMP Cytosol Deoxyribonucleic acid DNA Female Gene Expression Genetic aspects Genotyping Health aspects Host-Pathogen Interactions Human Genetics Human immunogenetics Humans Immunization Immunology India - epidemiology Male Mycobacterium tuberculosis - genetics Nucleotidyltransferases - genetics Nucleotidyltransferases - metabolism Patients Polymorphism, Single Nucleotide Recurrence Signal Transduction Single nucleotide polymorphisms Single-nucleotide polymorphism Tuberculosis Tuberculosis - enzymology Tuberculosis - genetics Tuberculosis - immunology Tuberculosis - microbiology Vaccination |
| title | 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 |
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