scholarly journals Effects of Lipopolysaccharide-Binding Protein (LBP) Single Nucleotide Polymorphism (SNP) in Infections, Inflammatory Diseases, Metabolic Disorders and Cancers

2021 ◽  
Vol 12 ◽  
Author(s):  
Leilei Meng ◽  
Zichen Song ◽  
Anding Liu ◽  
Uta Dahmen ◽  
Xiao Yang ◽  
...  
Keyword(s):  
Immune Response ◽  
Metabolic Disorders ◽  
Inflammatory Diseases ◽  
Binding Protein ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Main Component ◽  
The Impact ◽  
Lps Binding

Inflammation, which is induced by the immune response, is recognized as the driving factor in many diseases, including infections and inflammatory diseases, metabolic disorders and cancers. Genetic variations in pivotal genes associated with the immune response, particularly single nucleotide polymorphisms (SNPs), may account for predisposition and clinical outcome of diseases. Lipopolysaccharide (LPS)-binding protein (LBP) functions as an enhancer of the host response to LPS, the main component of the outer membrane of gram-native bacteria. Given the crucial role of LBP in inflammation, we will review the impact of SNPs in the LBP gene on infections and inflammatory diseases, metabolic disorders and cancers.

scholarly journals The role of polymorphic ERAP1 in autoinflammatory disease

2018 ◽  
Vol 38 (4) ◽  
Author(s):  
Emma Reeves ◽  
Edward James
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Autoinflammatory Disease ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Genetic Associations ◽  
Single Nucleotide ◽  
Cell Functions ◽  
The Impact

Autoimmune and autoinflammatory conditions represent a group of disorders characterized by self-directed tissue damage due to aberrant changes in innate and adaptive immune responses. These disorders possess widely varying clinical phenotypes and etiology; however, they share a number of similarities in genetic associations and environmental influences. Whilst the pathogenic mechanisms of disease remain poorly understood, genome wide association studies (GWAS) have implicated a number of genetic loci that are shared between several autoimmune and autoinflammatory conditions. Association of particular HLA alleles with disease susceptibility represents one of the strongest genetic associations. Furthermore, recent GWAS findings reveal strong associations with single nucleotide polymorphisms in the endoplasmic reticulum aminopeptidase 1 (ERAP1) gene and susceptibility to a number of these HLA-associated conditions. ERAP1 plays a major role in regulating the repertoire of peptides presented on HLA class I alleles at the cell surface, with the presence of single nucleotide polymorphisms in ERAP1 having a significant impact on peptide processing function and the repertoire of peptides presented. The impact of this dysfunctional peptide generation on CD8+ T-cell responses has been proposed as a mechanism of pathogenesis diseases where HLA and ERAP1 are associated. More recently, studies have highlighted a role for ERAP1 in innate immune-mediated pathways involved in inflammatory responses. Here, we discuss the role of polymorphic ERAP1 in various immune cell functions, and in the context of autoimmune and autoinflammatory disease pathogenesis.

Primer in Genetics and Genomics, Article 3–Explaining Human Diversity: The Role of DNA

2017 ◽  
Vol 19 (3) ◽  
pp. 350-356 ◽  
Author(s):  
Catherine Y. Read
Keyword(s):  
Deoxyribonucleic Acid ◽  
Copy Number Variations ◽  
Nucleotide Polymorphisms ◽  
Human Diversity ◽  
Single Nucleotide ◽  
Structural Alterations ◽  
Genetics And Genomics ◽  
Environmental Events ◽  
The Impact

Genetic variation lays the foundation for diversity and enables humans to adapt to changing environments. The order of the nucleotides adenine, guanine, cytosine, and thymine on the deoxyribonucleic acid (DNA) molecules of the nuclear chromosomes and mitochondrial DNA (mtDNA) plays an important role in normal cell division, tissue development, and reproduction but is susceptible to alteration from a large number of random, inherited, or environmental events. Variations can range from a change in a single nucleotide to duplication of entire chromosomes. Single nucleotide polymorphisms are the major source of human heterogeneity. Other variations that can alter phenotypes and adversely impact growth, development, and health include copy number variations, aneuploidies, and structural alterations such as deletions, translocations, inversions, duplications, insertions, or mutations in mtDNA. In addition, DNA rearrangements in somatic cells underlie the uncontrolled cell growth found in cancer. This article explores the mechanisms by which variations in DNA arise and the impact those changes can have on human health.

scholarly journals The role of the p53 tumor suppressor in metabolism and diabetes

2016 ◽  
Vol 231 (2) ◽  
pp. R61-R75 ◽  
Author(s):  
Che-Pei Kung ◽  
Maureen E Murphy
Keyword(s):  
Tumor Suppression ◽  
Metabolic Diseases ◽  
Nucleotide Polymorphisms ◽  
Review Of The Literature ◽  
Single Nucleotide ◽  
Cycle Arrest ◽  
Transcription Factor P53 ◽  
The Impact ◽  
The Relationship

In the context of tumor suppression, p53 is an undisputedly critical protein. Functioning primarily as a transcription factor, p53 helps fend off the initiation and progression of tumors by inducing cell cycle arrest, senescence or programmed cell death (apoptosis) in cells at the earliest stages of precancerous development. Compelling evidence, however, suggests that p53 is involved in other aspects of human physiology, including metabolism. Indeed, recent studies suggest that p53 plays a significant role in the development of metabolic diseases, including diabetes, and further that p53’s role in metabolism may also be consequential to tumor suppression. Here, we present a review of the literature on the role of p53 in metabolism, diabetes, pancreatic function, glucose homeostasis and insulin resistance. Additionally, we discuss the emerging role of genetic variation in the p53 pathway (single-nucleotide polymorphisms) on the impact of p53 in metabolic disease and diabetes. A better understanding of the relationship between p53, metabolism and diabetes may one day better inform the existing and prospective therapeutic strategies to combat this rapidly growing epidemic.

scholarly journals Promoter Polymorphisms of the Canine SCL11A1 Gene are Correlated with Susceptibility to Canine Leishmaniosis

2020 ◽  
Vol 70 (3) ◽  
pp. 305-315
Author(s):  
Isaia Symeonidou ◽  
Styliani Pappa ◽  
Elias Papadopoulos ◽  
Chrysostomos I. Dovas ◽  
Andreas Kourelis ◽  
...  
Keyword(s):  
Immune Response ◽  
Canine Leishmaniosis ◽  
Nucleotide Polymorphisms ◽  
Solute Carrier Family ◽  
Promoter Polymorphisms ◽  
Single Nucleotide ◽  
Prevalence Estimates ◽  
Solute Carrier ◽  
Determining Factor

AbstractIn enzootic areas the prevalence estimates of canine leishmaniosis are high whereas only a proportion of dogs exhibit the clinical disease, thus implying a role of host genetics. The type of the triggered immune response remains a crucial determining factor for the diverse outcome of this parasitosis. The Solute Carrier Family 11 member 1 (SLC11A1) is a protein, which plays a central role in macrophage function and is implicated in the regulation of the immune response. An extended study with 73 resistant and 75 susceptible to Leishmania dogs was conducted. A fragment of the promoter region of the canine SLC11A1 gene was amplified and digested providing the different genotypes for three previously recorded single-nucleotide polymorphisms (SNPs) (SNP1 T151C, SNP2 Α180G, SNP3 G318A) for each animal. Statistical analyses revealed that SNP2 Α180G in heterozygosity (AG) as well as SNP3 G318A in homozygosity (AA) are correlated with susceptibility to canine leishmaniosis.

Role of rs10406069 in miR-5196 in hyperdiploid childhood acute lymphoblastic leukemia

Epigenomics ◽  
2020 ◽  
Vol 12 (22) ◽  
pp. 1949-1955
Author(s):  
Angela Gutierrez-Camino ◽  
Chantal Richer ◽  
Pascal St-Onge ◽  
Elixabet Lopez-Lopez ◽  
Ana Carbone Bañeres ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Target Genes ◽  
Lymphoblastic Leukemia ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Mirna Genes ◽  
Relevant Role ◽  
The Impact

Aim: To determine the role of single nucleotide polymorphisms (SNPs) in noncoding RNAs in childhood acute lymphoblastic leukemia (ALL) subtypes. Materials & methods: We screened all SNPs in 130 pre-miRNA genes to assess their role in the susceptibility of the most common subtypes of ALL: hyperdiploid and ETV6-RUNX1. Results: In two independent cohorts, we found a significant association between rs10406069 in miR-5196 and the risk of developing hyperdiploid ALL. This observation could be explained by the impact of the SNP on miR-5196 expression and in turn, in its target genes. Indeed, rs10406069 was associated with expression changes in SMC1A, a gene involved in sister chromatin cohesion. Conclusion: rs10406069 in miR-5196 may have a relevant role in hyperdiploid ALL risk.

scholarly journals A mouse model of human TLR4 D299G/T399I SNPs reveals mechanisms of altered LPS and pathogen responses

2020 ◽  
Vol 218 (2) ◽  
Author(s):  
Katharina Richard ◽  
Kurt H. Piepenbrink ◽  
Kari Ann Shirey ◽  
Archana Gopalakrishnan ◽  
Shreeram Nallar ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Differential Susceptibility ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Tlr4 Signaling ◽  
The Impact ◽  
Signaling Efficiency

Two cosegregating single-nucleotide polymorphisms (SNPs) in human TLR4, an A896G transition at SNP rs4986790 (D299G) and a C1196T transition at SNP rs4986791 (T399I), have been associated with LPS hyporesponsiveness and differential susceptibility to many infectious or inflammatory diseases. However, many studies failed to confirm these associations, and transfection experiments resulted in conflicting conclusions about the impact of these SNPs on TLR4 signaling. Using advanced protein modeling from crystallographic data of human and murine TLR4, we identified homologous substitutions of these SNPs in murine Tlr4, engineered a knock-in strain expressing the D298G and N397I TLR4 SNPs homozygously, and characterized in vivo and in vitro responses to TLR4 ligands and infections in which TLR4 is implicated. Our data provide new insights into cellular and molecular mechanisms by which these SNPs decrease the TLR4 signaling efficiency and offer an experimental approach to confirm or refute human data possibly confounded by variables unrelated to the direct effects of the SNPs on TLR4 functionality.

scholarly journals ASSOCIATION OF POLYMORPHISM RS6737848 IN THE SOCS5 GENE WITH BRONCHIAL ASTHMA

2013 ◽  
Vol 68 (7) ◽  
pp. 53-56
Author(s):  
I. V. Saltykova ◽  
M. B. Freidin ◽  
E. Yu. Bragina ◽  
L. M. Ogorodova ◽  
V. P. Puzyrev
Keyword(s):  
Immune Response ◽  
Length Polymorphism ◽  
Additive Model ◽  
Dominant Model ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Restriction Fragments ◽  
Asthma Patients ◽  
Polymorphic Variants

Aim: to investigate the role of polymorphic variants of immune-response modifying genes in predisposition to asthma. Patients and methods. The analysis of restriction fragments length polymorphism was used to investigate 10 single-nucleotide polymorphisms: IFNG rs2069705, IFNGR2 rs17880053, IL4 rs 2070874, IL4RA rs 1805010, GATA3 rs10905277, TBX21 rs11652969, PIASY rs3760903, PIAS3 rs12756687, STAT5β rs16967593, and SOCS5 rs6737848 in 106 asthma patients and 115 healthy people. Results. The rs6737848 SOCS5 polymorphism was significantly associated with asthma in additive model (р =0,05, OR =0,338, 95%CI 0,158–0,723) and in dominant model (р =0,02, OR =0,284, CI 0,126–0,638). None of the polymorphisms of the studied genes was associated with total IgE levels. Conclusions. This is the first report on the association of rs6737848 SOCS5 with asthma. 

Association of genetic polymorphism of cytokines and antioxidant enzymes with the development of asbestosis

2020 ◽  
Vol 60 (12) ◽  
pp. 898-903
Author(s):  
Lyudmila P. Kuzmina ◽  
Anastasiya G. Khotuleva ◽  
Evgeniy V. Kovalevsky ◽  
Nikolay N. Anokhin ◽  
Iraklij M. Tskhomariya
Keyword(s):  
Antioxidant Enzymes ◽  
Genetic Polymorphism ◽  
Genetic Predisposition ◽  
Risk Groups ◽  
Dust Exposure ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Gstp1 Gene ◽  
Polymorphic Variants

Introduction. Various industries widely use chrysotile asbestos, which determines the relevance of research aimed at the prevention of asbestos-related diseases. It is promising to assess the role of specific genes, which products are potentially involved in the development and regulation of certain links in the pathogenesis of asbestosis, forming a genetic predisposition to the disease. The study aims to analyze the presence of associations of genetic polymorphism of cytokines and antioxidant enzymes with asbestosis development. Materials and methods. Groups were formed for examination among employees of OJSC "Uralasbest" with an established diagnosis of asbestosis and without lung diseases. For each person included in the study, dust exposure doses were calculated considering the percentage of time spent at the workplace during the shift for the entire work time. Genotyping of single nucleotide polymorphisms of cytokines IL1b (rs16944), IL4 (rs2243250), IL6 (rs1800795), TNFα (rs1800629) and antioxidant enzymes SOD2 (rs4880), GSTP1 (rs1610011), CAT (rs1001179) was carried out. Results. The authors revealed the associations of polymorphic variants A511G IL1b gene (OR=2.457, 95% CI=1.232-4.899) and C47T SOD2 gene (OR=1.705, 95% CI=1.055-2.756) with the development of asbestosis. There was an increase in the T allele IL4 gene (C589T) frequency in persons with asbestosis at lower values of dust exposure doses (OR=2.185, 95% CI=1.057-4.514). The study showed the associations of polymorphism C589T IL4 gene and C174G IL6 gene with more severe asbestosis, polymorphism A313G GSTP1 gene with pleural lesions in asbestosis. Conclusion. Polymorphic variants of the genes of cytokines and antioxidant enzymes, the protein products directly involved in the pathogenetic mechanisms of the formation of asbestosis, contribute to forming a genetic predisposition to the development and severe course of asbestosis. Using the identified genetic markers to identify risk groups for the development and intense period of asbestos-related pathology will optimize treatment and preventive measures, considering the organism's characteristics.

Hyperferritinaemia: An Iron Sword of Autoimmunity

2019 ◽  
Vol 25 (27) ◽  
pp. 2909-2918 ◽  
Author(s):  
Joanna Giemza-Stokłosa ◽  
Md. Asiful Islam ◽  
Przemysław J. Kotyla
Keyword(s):  
Immune Response ◽  
Macrophage Activation ◽  
Inflammatory Diseases ◽  
Acute Phase Reactant ◽  
Catastrophic Antiphospholipid Syndrome ◽  
Inflammatory Conditions ◽  
Phase Reactant ◽  
Signalling Molecule ◽  
Cytokine Synthesis

Background:: Ferritin is a molecule that plays many roles being the storage for iron, signalling molecule, and modulator of the immune response. Methods:: Different electronic databases were searched in a non-systematic way to find out the literature of interest. Results:: The level of ferritin rises in many inflammatory conditions including autoimmune disorders. However, in four inflammatory diseases (i.e., adult-onset Still’s diseases, macrophage activation syndrome, catastrophic antiphospholipid syndrome, and sepsis), high levels of ferritin are observed suggesting it as a remarkable biomarker and pathological involvement in these diseases. Acting as an acute phase reactant, ferritin is also involved in the cytokine-associated modulator of the immune response as well as a regulator of cytokine synthesis and release which are responsible for the inflammatory storm. Conclusion:: This review article presents updated information on the role of ferritin in inflammatory and autoimmune diseases with an emphasis on hyperferritinaemic syndrome.

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