Comparative Genetic Association Analysis of Human Genetic Susceptibility to Pulmonary and Lymph Node Tuberculosis

Abhimanyu; Mridula Bose; Astha Giri; Mandira Varma-Basil

doi:10.3390/genes14010207

Comparative Genetic Association Analysis of Human Genetic Susceptibility to Pulmonary and Lymph Node Tuberculosis

Genes (Basel). 2023 Jan 13;14(1):207. doi: 10.3390/genes14010207.

Authors

Abhimanyu^{1

2}, Mridula Bose¹, Astha Giri¹, Mandira Varma-Basil¹

Affiliations

¹ Department of Microbiology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi 110007, India.
² The Global Tuberculosis Program, Baylor College of Medicine, William T Shearer Center for Immunobiology, Texas Children's Hospital, Houston, TX 77004, USA.

Abstract

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.

Keywords: cytokine; extra-pulmonary tuberculosis; genetic association; genotype; innate immunity; lymph node tuberculosis; pulmonary tuberculosis; serum; single nucleotide polymorphisms.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cytokines / genetics
Genetic Predisposition to Disease
Humans
Interleukin-12 / genetics
Interleukin-4 / genetics
Lung
Polymorphism, Single Nucleotide
Toll-Like Receptor 2 / genetics
Tuberculosis, Lymph Node*
Tuberculosis, Pulmonary* / genetics

Substances

Toll-Like Receptor 2
Interleukin-4
Cytokines
Interleukin-12

Grants and funding

This research was funded by Council for Scientific and Industrial Research; Government of India funded the Research and Fellowship for Abhimanyu via Grant Number: 60(0081 EMR-II. The research was also supported by Indian council of medical research (ICMR) grant No. 5/8/5/14/2012-ECD-1 for the work on SP110 and a Senior Research fellowship to Abhimanyu. The authors also acknowledge an Emeritus Professor Fellowship to Mridula Bose from ICMR.