Comparative Genetic Association Analysis of Human Genetic Susceptibility to Pulmonary and Lymph Node Tuberculosis
Background: Tuberculosis (TB) manifests itself primarily in the lungs as pulmonary disease (PTB) and sometimes disseminates to other organs to cause extra-pulmonary TB, such as lymph node TB (LNTB). This study aimed to investigate the role of host genetic polymorphism in immunity related genes to fi...
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MDPI AG
2023-01-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/14/1/207 |
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| author | Abhimanyu Mridula Bose Astha Giri Mandira Varma-Basil |
| author_facet | Abhimanyu Mridula Bose Astha Giri Mandira Varma-Basil |
| author_sort | Abhimanyu |
| collection | DOAJ |
| description | Background: Tuberculosis (TB) manifests itself primarily in the lungs as pulmonary disease (PTB) and sometimes disseminates to other organs to cause extra-pulmonary TB, such as lymph node TB (LNTB). This study aimed to investigate the role of host genetic polymorphism in immunity related genes to find a genetic basis for such differences. Methods: Sixty-three, Single nucleotide polymorphisms (SNPs) in twenty-three, TB-immunity related genes including eleven innate immunity (<i>SLCA11</i>, <i>VDR</i>, <i>TLR2</i>, <i>TLR4</i>, <i>TLR8</i>, <i>IRGM</i>, <i>P2RX7</i>, <i>LTA4H</i>, <i>SP110</i>, <i>DCSIGN and NOS2A</i>) and twelve cytokine (TNFA, <i>IFNG</i>, <i>IL2</i>, <i>Il12</i>, <i>IL18</i>, <i>IL1B</i>, <i>IL10</i>, <i>IL6</i>, <i>IL4</i>, <i>rs1794068</i>, <i>IL8 and TNFB</i>) genes were investigated to find genetic associations in both PTB and LNTB as compared to healthy community controls. The serum cytokine levels were correlated for association with the genotypes. Results: PTB and LNTB showed differential genetic associations. The genetic variants in the cytokine genes (<i>IFNG</i>, <i>IL12</i>, <i>IL4</i>, <i>TNFB</i> and <i>IL1RA</i> and <i>TLR2</i>, <i>4</i> associated with PTB susceptibility and cytokine levels but not LNTB (<i>p</i> < 0.05). Similarly, genetic variants in <i>LTA4H</i>, <i>P2RX7</i>, <i>DCSIGN</i> and <i>SP110</i> showed susceptibility to LNTB and not PTB. Pathway analysis showed abundance of cytokine related variants for PTB and apoptosis related variants for LNTB. Conclusions: PTB and LNTB outcomes of TB infection have a genetic component and should be considered for any future functional studies or studies on susceptibility to pulmonary and extra-pulmonary TB. |
| first_indexed | 2024-03-09T12:34:33Z |
| format | Article |
| id | doaj.art-1ae0bdeaffe34663a40049415301670a |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-09T12:34:33Z |
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| spelling | doaj.art-1ae0bdeaffe34663a40049415301670a2023-11-30T22:25:11ZengMDPI AGGenes2073-44252023-01-0114120710.3390/genes14010207Comparative Genetic Association Analysis of Human Genetic Susceptibility to Pulmonary and Lymph Node TuberculosisAbhimanyu0Mridula Bose1Astha Giri2Mandira Varma-Basil3Department of Microbiology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi 110007, IndiaDepartment of Microbiology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi 110007, IndiaDepartment of Microbiology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi 110007, IndiaDepartment of Microbiology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi 110007, IndiaBackground: Tuberculosis (TB) manifests itself primarily in the lungs as pulmonary disease (PTB) and sometimes disseminates to other organs to cause extra-pulmonary TB, such as lymph node TB (LNTB). This study aimed to investigate the role of host genetic polymorphism in immunity related genes to find a genetic basis for such differences. Methods: Sixty-three, Single nucleotide polymorphisms (SNPs) in twenty-three, TB-immunity related genes including eleven innate immunity (<i>SLCA11</i>, <i>VDR</i>, <i>TLR2</i>, <i>TLR4</i>, <i>TLR8</i>, <i>IRGM</i>, <i>P2RX7</i>, <i>LTA4H</i>, <i>SP110</i>, <i>DCSIGN and NOS2A</i>) and twelve cytokine (TNFA, <i>IFNG</i>, <i>IL2</i>, <i>Il12</i>, <i>IL18</i>, <i>IL1B</i>, <i>IL10</i>, <i>IL6</i>, <i>IL4</i>, <i>rs1794068</i>, <i>IL8 and TNFB</i>) genes were investigated to find genetic associations in both PTB and LNTB as compared to healthy community controls. The serum cytokine levels were correlated for association with the genotypes. Results: PTB and LNTB showed differential genetic associations. The genetic variants in the cytokine genes (<i>IFNG</i>, <i>IL12</i>, <i>IL4</i>, <i>TNFB</i> and <i>IL1RA</i> and <i>TLR2</i>, <i>4</i> associated with PTB susceptibility and cytokine levels but not LNTB (<i>p</i> < 0.05). Similarly, genetic variants in <i>LTA4H</i>, <i>P2RX7</i>, <i>DCSIGN</i> and <i>SP110</i> showed susceptibility to LNTB and not PTB. Pathway analysis showed abundance of cytokine related variants for PTB and apoptosis related variants for LNTB. Conclusions: PTB and LNTB outcomes of TB infection have a genetic component and should be considered for any future functional studies or studies on susceptibility to pulmonary and extra-pulmonary TB.https://www.mdpi.com/2073-4425/14/1/207pulmonary tuberculosislymph node tuberculosisextra-pulmonary tuberculosissingle nucleotide polymorphismscytokineinnate immunity |
| spellingShingle | Abhimanyu Mridula Bose Astha Giri Mandira Varma-Basil Comparative Genetic Association Analysis of Human Genetic Susceptibility to Pulmonary and Lymph Node Tuberculosis Genes pulmonary tuberculosis lymph node tuberculosis extra-pulmonary tuberculosis single nucleotide polymorphisms cytokine innate immunity |
| title | Comparative Genetic Association Analysis of Human Genetic Susceptibility to Pulmonary and Lymph Node Tuberculosis |
| title_full | Comparative Genetic Association Analysis of Human Genetic Susceptibility to Pulmonary and Lymph Node Tuberculosis |
| title_fullStr | Comparative Genetic Association Analysis of Human Genetic Susceptibility to Pulmonary and Lymph Node Tuberculosis |
| title_full_unstemmed | Comparative Genetic Association Analysis of Human Genetic Susceptibility to Pulmonary and Lymph Node Tuberculosis |
| title_short | Comparative Genetic Association Analysis of Human Genetic Susceptibility to Pulmonary and Lymph Node Tuberculosis |
| title_sort | comparative genetic association analysis of human genetic susceptibility to pulmonary and lymph node tuberculosis |
| topic | pulmonary tuberculosis lymph node tuberculosis extra-pulmonary tuberculosis single nucleotide polymorphisms cytokine innate immunity |
| url | https://www.mdpi.com/2073-4425/14/1/207 |
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