PMID- 36672948
OWN - NLM
STAT- MEDLINE
DCOM- 20230124
LR  - 20230201
IS  - 2073-4425 (Electronic)
IS  - 2073-4425 (Linking)
VI  - 14
IP  - 1
DP  - 2023 Jan 13
TI  - Comparative Genetic Association Analysis of Human Genetic Susceptibility to 
      Pulmonary and Lymph Node Tuberculosis.
LID - 10.3390/genes14010207 [doi]
LID - 207
AB  - 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 (SLCA11, VDR, TLR2, TLR4, TLR8, IRGM, P2RX7, LTA4H, SP110, DCSIGN and 
      NOS2A) and twelve cytokine (TNFA, IFNG, IL2, Il12, IL18, IL1B, IL10, IL6, IL4, 
      rs1794068, IL8 and TNFB) 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 (IFNG, IL12, IL4, TNFB and IL1RA and TLR2, 4 associated with PTB 
      susceptibility and cytokine levels but not LNTB (p < 0.05). Similarly, genetic 
      variants in LTA4H, P2RX7, DCSIGN and SP110 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.
FAU - Abhimanyu
AU  - Abhimanyu
AUID- ORCID: 0000-0001-7888-8722
AD  - Department of Microbiology, Vallabhbhai Patel Chest Institute, University of 
      Delhi, Delhi 110007, India.
AD  - The Global Tuberculosis Program, Baylor College of Medicine, William T Shearer 
      Center for Immunobiology, Texas Children's Hospital, Houston, TX 77004, USA.
FAU - Bose, Mridula
AU  - Bose M
AD  - Department of Microbiology, Vallabhbhai Patel Chest Institute, University of 
      Delhi, Delhi 110007, India.
FAU - Giri, Astha
AU  - Giri A
AD  - Department of Microbiology, Vallabhbhai Patel Chest Institute, University of 
      Delhi, Delhi 110007, India.
FAU - Varma-Basil, Mandira
AU  - Varma-Basil M
AUID- ORCID: 0000-0001-5562-015X
AD  - Department of Microbiology, Vallabhbhai Patel Chest Institute, University of 
      Delhi, Delhi 110007, India.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230113
PL  - Switzerland
TA  - Genes (Basel)
JT  - Genes
JID - 101551097
RN  - 0 (Toll-Like Receptor 2)
RN  - 207137-56-2 (Interleukin-4)
RN  - 0 (Cytokines)
RN  - 187348-17-0 (Interleukin-12)
SB  - IM
MH  - Humans
MH  - Genetic Predisposition to Disease
MH  - *Tuberculosis, Pulmonary/genetics
MH  - Toll-Like Receptor 2/genetics
MH  - Interleukin-4/genetics
MH  - *Tuberculosis, Lymph Node
MH  - Cytokines/genetics
MH  - Polymorphism, Single Nucleotide
MH  - Interleukin-12/genetics
MH  - Lung
PMC - PMC9859508
OTO - NOTNLM
OT  - cytokine
OT  - extra-pulmonary tuberculosis
OT  - genetic association
OT  - genotype
OT  - innate immunity
OT  - lymph node tuberculosis
OT  - pulmonary tuberculosis
OT  - serum
OT  - single nucleotide polymorphisms
COIS- The authors declare no conflict of interest. The funders had no role in study 
      design, data collection and analysis, decision to publish, or preparation of the 
      manuscript. Some of the results were submitted to the funders as a part of the 
      final project report. This work was part of doctoral thesis of Dr. Abhimanyu, Th 
      19865, University of Delhi. This work has been presented as poster at the Indian 
      Society for Human Genetics conference by Dr Abhimanyu and at the Indian 
      association of medical microbiologist meeting by Astha Giri.
EDAT- 2023/01/22 06:00
MHDA- 2023/01/25 06:00
PMCR- 2023/01/13
CRDT- 2023/01/21 01:15
PHST- 2022/11/04 00:00 [received]
PHST- 2023/01/08 00:00 [revised]
PHST- 2023/01/11 00:00 [accepted]
PHST- 2023/01/21 01:15 [entrez]
PHST- 2023/01/22 06:00 [pubmed]
PHST- 2023/01/25 06:00 [medline]
PHST- 2023/01/13 00:00 [pmc-release]
AID - genes14010207 [pii]
AID - genes-14-00207 [pii]
AID - 10.3390/genes14010207 [doi]
PST - epublish
SO  - Genes (Basel). 2023 Jan 13;14(1):207. doi: 10.3390/genes14010207.