Dataset Information

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

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.

SUBMITTER: Abhimanyu

PROVIDER: S-EPMC9859508 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Publications

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

Abhimanyu Bose Mridula M Giri Astha A Varma-Basil Mandira M

Genes 20230113 1

<h4>Background</h4>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.<h4>Methods</h4>Sixty-three, Single nucleotide polymorphisms (SNPs) in twenty-three, TB-immunity related genes including eleven innate immunity (<i>SLCA1 ...[more]

PMID: 36672948

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Project description:Understanding how the bacteriomes in tuberculous lesions can be influenced by the susceptibility of Mycobacterium tuberculosis (MTB) can provide valuable information for preventing and treating drug resistant tuberculosis (DR-TB). High-throughput 16S rRNA sequencing was employed to analyze the bacteriome in pulmonary TB lesions from 14 patients with DR-TB and 47 patients with drug sensitive tuberculosis (DS-TB), along with 18 normal lung tissues (NT) from 18 lung cancer patients serving as the bacterial baseline. The phylogenetic investigation of communities by reconstruction of unobserved states2 (PICRUSt2) algorithm was utilized to predict bacterial metabolic functions. The major phyla of pulmonary bacteriomes included Proteobacteria, Actinobacteria, Bacteroidetes, Firmicutes and Fusobacteria. Alpha diversity indices, including ACE, Chao1, Shannon and OTU observed, all demonstrated different bacterial communities of DS-TB samples from that of NT samples; while only Shannon indicated difference between DR-TB and NT samples. The analysis of similarity (ANOSIM) showed significantly different bacterial communities within TB lesions compared to NT samples (R = 0.418, p = 0.001). However, difference was not observed between DR-TB and DS-TB samples (ANOSIM, R = 0.069, p = 0.173). The bacterial profiles within each DR-TB individual appeared unique, with no obvious clusters corresponding to drug-resistant phenotypes. Nevertheless, indicator genera identified in DR-TB and DS-TB lesions demonstrated distinctive micro-ecological environments. Most COG functions were enriched in TB lesions, and the most significant one was [J] translation, ribosomal structure and biogenesis. The distinct enrichment patterns of bacterial enzymes in DR-TB and DS-TB lesions suggest that pulmonary bacterial activities can be modulated by the susceptibility of MTB bacilli. This study provides fresh perspectives and strategies for the precise diagnosis and assessment of drug resistance tuberculosis.

Project description:ObjectivesTo investigate the clinical epidemiological and drug resistance (DR) characteristics of lymph node tuberculosis (LNTB) in Hunan Province which locates in South-central China, and to provide scientific clues for effective prevention and treatment of LNTB.MethodsWe retrospectively collected LNTB patients with Mycobacterium tuberculosis culture positive at Hunan Chest Hospital, the biggest TB reference hospital in South-central China, from January 2013 to December 2021. The multiple demographic, clinical and drug susceptibility data of patients were collected from the hospital's electronic patient records. Descriptive statistical methods, Chi-square test and logistic regression analysis were employed as statistical methods.ResultsOf the 577 LNTB cases, 373 (64.64%) were males, 352 (61.01%) were farmers; majority (161, 33.10%) aged at 20-29 years old; 147 (25.48%) had simple LNTB, 350 (60.66%) had LNTB combined with pulmonary TB (PTB) (defined as LNTB-PTB), and 80 (13.86%) had LNTB combined with other extrapulmonary TB (EPTB) (defined as LNTB-EPTB). A total of 345 (59.79%, 345/577) LNTB patients had cervical node infection, and the simple LNTB patients (81.63%, 120/147) had higher proportion of this infection than LNTB-PTB (51.71%, 181/350) and LNTB-EPTB (55.00%, 44/80) (both p values <0.017), respectively. LNTB-EPTB was more inclined to have abdominal tuberculous LNs (20%, 16/80) and at least four tuberculous lesions (22.50%, 18/80) than simple LNTB and LNTB-PTB. Seventy-seven (13.34%) and 119 (20.62%) were resistant to rifampicin (RIF) and isoniazid (INH), respectively; 72 (12.48%) were multi-drug resistant (MDR), and a total of 150 (26.00%) were DR (resistant to at least one of RIF, INH, ethambutol and streptomycin). LNTB patients aged 30-34 and 50-54 years old (compared to those aged <30 years) were independent predictors of RIF resistance (RR) (ORs were 3.47 and 2.83, respectively; 95% CIs were 1.64-7.35 and 1.08-7.46, respectively).ConclusionOur study disclosed the epidemiological and DR characteristics of LNTB in Hunan Province, China. High LNTB prevalence was found in younger people while high RR LNTB prevalence was found in older ones, suggesting that we should conduct further studies to clarify the occurrence of RR in LNTB, meanwhile, strengthen the diagnoses and treatments of LNTB to prevent the emergence of RR.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

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