Immune-related gene polymorphisms in pulmonary diseases

Singh, D. P.; Bagam, Prathyusha; Sahoo, Malaya K.; Batra, Sanjay

doi:10.1016/j.tox.2017.03.020

Cited by 15 publications

(13 citation statements)

References 145 publications

(142 reference statements)

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“…50 Numerous SNPs in alpha 1-antitrypsin, tumor necrosis factor, microsomal epoxide hydrolase, glutathione S-transferase, interleukin-6, interleukin-8 genes have been studied in terms of association with COPD susceptibility, severity, phenotypes, drug response, or comorbidities, but with conflicting results and limitations of the studies. 51,52 In 2009, two case-control studies comprising 1488 participants, conducted by He et al 30 revealed that out of seven IL-6 SNPs, four were associated with COPD, while the rs1800797 allele was associated with a rapid decline in lung function. Another European study investigated the relationship between rs1800797, rs1800795, and rs1800796 and the susceptibility for the disease, the lung function, and hypoxemia level and concluded that rs1800797 and rs1800795 were not associated with the disease, the frequency of genotypes containing the C allele was lower in COPD patients, and also that the GCG (-597, -174, -572) haplotype was associated with the disease.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-6 serum level and -597 A/G gene polymorphism in moderate and severe chronic obstructive pulmonary disease

et al. 2020

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Inflammation is a major pathogenic pathway in pulmonary chronic obstructive disease (COPD). Interleukin-6 (IL-6) mediates the local and systemic immune response. The aim consisted in investigating the relationship between IL-6 serum levels and IL-6 -597A/G gene polymorphism (rs1800797) with COPD. Serum levels of IL-6 were determined using an enzyme-linked immune-sorbent assay, in 120 participants (60 COPD patients and 60 healthy subjects), from Transylvanian region. The IL-6 -597A/G gene polymorphism was investigated by high molecular weight genomic DNA extracted from the peripheral blood leukocytes, and subsequently analyzed by the Polymerase Chain Reaction Restriction Fragment Length Polymorphism (PCR-RFLP) technique. Smoking history, the severity of the disease, expressed by the GOLD stages, and arterial blood partial pressure of oxygen (PaO2) levels were also investigated. COPD patients had significantly elevated blood levels of IL-6 when compared to the control group ( p < 0.05). The frequencies of AA, AG, and GG genotypes were 61.6%, 26.6%, and 11.6% in the COPD cases and 70%, 23.3%, and 6.7% in healthy subjects, respectively. There were no statistically significant differences in IL-6 rs1800797 genotypes and allele frequencies between cases and controls ( χ2 = 0.54, OR = 1.29 and χ2 = 0.21, OR = 1.48, respectively). Higher serum levels of IL-6 were found in the GG genotype subgroup in COPD patients. IL 6 levels are higher in COPD patients, where positively correlate with pack-year index, but not with clinical features. Although COPD patients did not have statistically different rs1800797 allele distribution compared to healthy subjects, the GG genotype is associated with higher IL6 serum levels.

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Section: Discussionmentioning

confidence: 99%

Interleukin-6 serum level and -597 A/G gene polymorphism in moderate and severe chronic obstructive pulmonary disease

et al. 2020

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“…; obtained from ATCC) using TaqMan Gene expression assays (Thermo Fisher) for the NLRP1 , NLRP4 , and NLRP8 genes. The WI38 cell line was selected for the study because fibroblasts are believed to be the major cells responsible for the production and maintenance of the extracellular matrix, and fibroblasts from individuals with COPD have a reduced capability to sustain tissue repair [18]. The total RNA, from blood, was extracted using Trizol.…”

Section: Methodsmentioning

confidence: 99%

Association of NLRP1 Coding Polymorphism with Lung Function and Serum IL-1β Concentration in Patients Diagnosed with Chronic Obstructive Pulmonary Disease (COPD)

Ozretić

Filho

Catalano

et al. 2019

Genes

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Chronic obstructive pulmonary disease (COPD) is a chronic disease characterized by a progressive decline in lung function due to airflow limitation, mainly related to IL-1β-induced inflammation. We have hypothesized that single nucleotide polymorphisms (SNPs) in NLRP genes, coding for key regulators of IL-1β, are associated with pathogenesis and clinical phenotypes of COPD. We recruited 704 COPD individuals and 1238 healthy controls for this study. Twenty non-synonymous SNPs in 10 different NLRP genes were genotyped. Genetic associations were estimated using logistic regression, adjusting for age, gender, and smoking history. The impact of genotypes on patients’ overall survival was analyzed with the Kaplan–Meier method with the log-rank test. Serum IL-1β concentration was determined by high sensitivity assay and expression analysis was done by RT-PCR. Decreased lung function, measured by a forced expiratory volume in 1 s (FEV1% predicted), was significantly associated with the minor allele genotypes (AT + TT) of NLRP1 rs12150220 (p = 0.0002). The same rs12150220 genotypes exhibited a higher level of serum IL-1β compared to the AA genotype (p = 0.027) in COPD patients. NLRP8 rs306481 minor allele genotypes (AG + AA) were more common in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) definition of group A (p = 0.0083). Polymorphisms in NLRP1 (rs12150220; OR = 0.55, p = 0.03) and NLRP4 (rs12462372; OR = 0.36, p = 0.03) were only nominally associated with COPD risk. In conclusion, coding polymorphisms in NLRP1 rs12150220 show an association with COPD disease severity, indicating that the fine-tuning of the NLRP1 inflammasome could be important in maintaining lung tissue integrity and treating the chronic inflammation of airways.

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“…One particularly powerful approach to assess the role of some processes in humans is to investigate whether genetic variation influences susceptibility to infection. Single Nucleotide Polymorphisms (SNPs) are believed to be the true source of variability among humans (Pacheco and Moraes, 2009;Singh et al, 2017) and it is expected that the variants in genes involved in the pathogen-host interaction are influencing resistance/ susceptibility to the disease. Some reports have investigated SNPs in genes involved in the autophagy process, leading to important evidence about its role during human TB.…”

Section: Genetic Association Studies In Autophagy-related Genesmentioning

confidence: 99%

Shedding Light on Autophagy During Human Tuberculosis. A Long Way to Go

Pellegrini

Tateosian

Morelli

et al. 2022

Front. Cell. Infect. Microbiol.

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Immunity against Mycobacterium tuberculosis (Mtb) is highly complex, and the outcome of the infection depends on the role of several immune mediators with particular temporal dynamics on the host microenvironment. Autophagy is a central homeostatic mechanism that plays a role on immunity against intracellular pathogens, including Mtb. Enhanced autophagy in macrophages mediates elimination of intracellular Mtb through lytic and antimicrobial properties only found in autolysosomes. Additionally, it has been demonstrated that standard anti-tuberculosis chemotherapy depends on host autophagy to coordinate successful antimicrobial responses to mycobacteria. Notably, autophagy constitutes an anti-inflammatory mechanism that protects against endomembrane damage triggered by several endogenous components or infectious agents and precludes excessive inflammation. It has also been reported that autophagy can be modulated by cytokines and other immunological signals. Most of the studies on autophagy as a defense mechanism against Mycobacterium have been performed using murine models or human cell lines. However, very limited information exists about the autophagic response in cells from tuberculosis patients. Herein, we review studies that face the autophagy process in tuberculosis patients as a component of the immune response of the human host against an intracellular microorganism such as Mtb. Interestingly, these findings might contribute to recognize new targets for the development of novel therapeutic tools to combat Mtb. Actually, either as a potential successful vaccine or a complementary immunotherapy, efforts are needed to further elucidate the role of autophagy during the immune response of the human host, which will allow to achieve protective and therapeutic benefits in human tuberculosis.

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Immune-related gene polymorphisms in pulmonary diseases

Cited by 15 publications

References 145 publications

Interleukin-6 serum level and -597 A/G gene polymorphism in moderate and severe chronic obstructive pulmonary disease

Interleukin-6 serum level and -597 A/G gene polymorphism in moderate and severe chronic obstructive pulmonary disease

Association of NLRP1 Coding Polymorphism with Lung Function and Serum IL-1β Concentration in Patients Diagnosed with Chronic Obstructive Pulmonary Disease (COPD)

Shedding Light on Autophagy During Human Tuberculosis. A Long Way to Go

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