Variants of the IFI16 Gene Affecting the Levels of Expression of mRNA Are Associated with Susceptibility to Behçet Disease

Objective.Behçet disease (BD) is a multifactorial disease in which infectious agents have been proposed as triggers in genetically predisposed individuals. The aim of our study was to investigate the role of innate immunity receptors, specifically the nucleic acid sensors, in susceptibility to BD.Methods.Seventy-four tag single nucleotide polymorphisms (tSNP) selected in 9 candidate genes (DDX58, IFIH1, TLR3, TLR7, TLR8, AIM2, IFI16, ZBP1, and TLR9) were genotyped in 371 patients and 854 controls. Assays of mRNA expression and allele-specific transcript quantification (ASTQ) were performed in 110 and 50 controls, respectively.Results.Patients and controls were genotyped and 2 tSNP (rs6940 in IFI16 and rs855873 in AIM2) were associated with BD. To confirm this association, these tSNP were genotyped in 850 additional controls, and the total cohort was randomly divided into 2 cohorts. The association of these 2 tSNP with the disease remained in both cohorts. One haplotype (rs6940T-rs855873G) was identified as a risk factor (OR 1.41, 95% CI 1.06–1.86, p = 0.015), and another (rs6940A-rs855873A) as a protective factor (OR 0.65, 95% CI 0.47–0.90, p = 0.009). Samples with the risk haplotype had lower IFI16 expression levels than samples with the protective (0.99 ± 0.29 vs 1.23 ± 0.50, p = 0.022). Consistently, in the ASTQ assays performed with the nonsynonymous rs6940 SNP, the risk allele had lower IFI16 expression levels than the protective (p = 0.027).Conclusion.Our findings suggest association of IFI16, a cytosolic sensor of dsDNA and mediator of the AIM2 inflammasome-dependent pathway, in susceptibility to BD. Differences genetically determined in the levels of this molecule could be the cause of this association.

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The role of T cells and interleukin‐17A in Behçet disease

British Journal of Dermatology ◽

10.1111/bjd.20788 ◽

2021 ◽

Vol 185 (6) ◽

Keyword(s):

T Cells ◽

Behçet Disease ◽

Behcet Disease ◽

Interleukin 17A

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The role of infections in Behçet disease and neuro-Behçet syndrome

Autoimmunity Reviews ◽

10.1016/j.autrev.2015.02.009 ◽

2015 ◽

Vol 14 (7) ◽

pp. 609-615 ◽

Cited By ~ 11

Author(s):

Monica Marta ◽

Ernestina Santos ◽

Ester Coutinho ◽

Ana Martins Silva ◽

João Correia ◽

...

Keyword(s):

Behçet Disease ◽

Behcet Disease ◽

Behçet Syndrome ◽

Behcet Syndrome

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The investigation of BTLA single-nucleotide polymorphisms in patients with Behcet disease in Elazıg province

Turkish Journal of Biochemistry ◽

10.1515/tjb-2019-0221 ◽

2020 ◽

Vol 45 (3) ◽

pp. 323-327

Author(s):

Yasin Cetin ◽

Nafiye Fulya Ilhan ◽

Deniz Sen ◽

Sevim Karakas Celik

Keyword(s):

Lymphocyte Activation ◽

Behçet Disease ◽

Nucleotide Polymorphisms ◽

Behcet Disease ◽

Gene Encoding ◽

Mortality And Morbidity ◽

Significant Difference ◽

Pcr Rflp ◽

Risk Of Disease ◽

And Control

AbstractObjectiveBehcet Disease (BD) is a systemic chronic autoinflammatory disorder that significantly increases mortality and morbidity. Although B- and T-lymphocyte attenuator (BTLA) is important in regulating lymphocyte activation during inflammation and infection, it is unclear whether any polymorphism in the gene encoding the BTLA is associated with autoimmune diseases and cancer. The goal of the study was to research the relationship between the alleles, genotypes and haplotypes frequencies of chosen BTLA gene polymorphisms (rs184489 and rs9288952) and the risk of Behcet disease.Materials and methodsThe population of this study consisted of 108 patients with BD and 108 healthy controls. Genotyping for the rs184489 and rs9288952 polymorphisms were performed using PCR-RFLP method.ResultsIn terms of genotype and allele frequencies between the patient and control groups, there were no statistically significant differences (p > 0.05). However, there was a statistically significant difference in haplotype analysis between the two groups (p = 0.001). Moreover, carrying the T allele for the rs1844089 polymorphism and C allele for the rs9288952 polymorphism increase the risk of disease.ConclusionOur findings propose that CT haplotype might have a potential function in the susceptibility to BD.

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HLA RNAseq reveals high allele-specific variability in mRNA expression

10.1101/413534 ◽

2018 ◽

Cited By ~ 1

Author(s):

Tiira Johansson ◽

Dawit A. Yohannes ◽

Satu Koskela ◽

Jukka Partanen ◽

Päivi Saavalainen

Keyword(s):

Autoimmune Diseases ◽

Mrna Expression ◽

Allelic Variation ◽

Healthy Individuals ◽

Specific Expression ◽

Allele Specific Expression ◽

Hla Alleles ◽

Expression Levels ◽

Allele Specific

AbstractThe HLA gene complex is the most important, single genetic factor in susceptibility to most diseases with autoimmune or autoinflammatory origin and in transplantation matching. The majority of the studies have focused on the huge allelic variation in these genes; only a few studies have explored differences in expression levels of HLA alleles. To study the expression levels of HLA alleles more systematically we utilised two different RNA sequencing methods. Illumina RNAseq has a high sequencing accuracy and depth but is limited by the short read length, whereas Oxford Nanopore’s technology can sequence long templates, but has a poor accuracy. We studied allelic mRNA levels of HLA class I and II alleles from peripheral blood samples of 50 healthy individuals. The results demonstrate large differences in mRNA expression levels between HLA alleles. The method can be applied to quantitate the expression differences of HLA alleles in various tissues and to evaluate the role of this type of variation in transplantation matching and susceptibility to autoimmune diseases.Author SummaryEven though HLA is widely studied less is known of its allele-specific expression. Due to the pivotal role of HLA in infection response, autoimmunity, and transplantation biology its expression surely must play a part as well. In hematopoietic stem cell transplantation the challenge often is to find a suitable HLA-matched donor due to the high allelic variation. Classical HLA typing methods do not take into account HLA allele-specific expression. However, differential allelic expression levels could be crucial in finding permissive mismatches in order to save a patient’s life. Additionally, differential HLA expression levels can lead into beneficial impact in viral clearance but also undesirable effects in autoimmune diseases. To study HLA expression we developed a novel RNAseq-based method to systematically characterize allele-specific expression levels of classical HLA genes. We tested our method in a set of 50 healthy individuals and found differential expression levels between HLA alleles as well as interindividual variability at the gene level. Since NGS is already well adopted in HLA research the next step could be to determine HLA allele-specific expression in addition to HLA allelic variation and HLA-disease association studies in various cells, tissues, and diseases.

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Genetics and epigenetics of pelvic organs prolapse

Medical alphabet ◽

10.33667/2078-5631-2019-4-33(408)-44-47 ◽

2020 ◽

Vol 4 (33) ◽

pp. 44-47

Author(s):

D. S. Titov ◽

G. B. Dikke

Keyword(s):

Clinical Symptoms ◽

Lysyl Oxidase ◽

Pelvic Organ ◽

Response To Treatment ◽

Risk Haplotype ◽

Gene Suppression ◽

Genes Encoding ◽

Risk Prognosis ◽

Genetically Determined

Identification of the genetic variants underlying the heredity of pelvic organ prolapse helps to identify useful markers for assessing clinical risk, prognosis and response to treatment. An association of polymorphisms in the ADRB 3 gene with an overactive bladder and in the COL1A1 gene with PTO was detected. AA mutation of the COL3A1 rs1800255 genotype increases the probability of VET by 4.8 times. There is evidence of involvement in the development of PTO genes of the extracellular matrix degradation group (ECM), which includes genes encoding matrix metalloproteinases. During the study of diseases of the connective tissue, their syntropy was revealed, which is genetically determined as a common risk haplotype of the FBLN 5 gene. The significance of epigenetic mechanisms for the development of VET is shown in the form of lysyl oxidase (LO) gene suppression. So far, the role of factors that induce changes in epigenetic regulation and lead to the appearance of clinical symptoms of prolapse is not clear.

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Possible role of progranulin in Behçet disease

Journal of the American Academy of Dermatology ◽

10.1016/j.jaad.2019.06.406 ◽

2019 ◽

Vol 81 (4) ◽

pp. AB106

Keyword(s):

Behçet Disease ◽

Behcet Disease

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Role of microRNA 4717, its effects on programmed cell death protein-1 in hepatitis B infection, and interaction between PDCD1 and miR-4717

European Journal of Inflammation ◽

10.1177/2058739220934604 ◽

2020 ◽

Vol 18 ◽

pp. 205873922093460

Author(s):

Junhua Li ◽

Andong Li

Keyword(s):

Cell Death ◽

Hepatitis B ◽

Programmed Cell Death ◽

Quantitative Polymerase Chain Reaction ◽

Nucleotide Polymorphisms ◽

Tissue Samples ◽

Expression Levels ◽

Si Rna ◽

Cell Death Protein

It is suggested that programmed cell death protein-1 (PD-1) is involved in hepatitis B virus (HBV) infection, the leading cause of hepatocellular carcinoma globally. This study was multi-aimed, that is, to investigate the role of microRNA (miR) 4717 and its target, PD-1 and to determine how the rs10204525 polymorphism in the 3′ untranslated region (3′UTR) of PD-1 affects its interaction with miR-4717. The expression levels of miR-4717 with various single-nucleotide polymorphisms were measured by reverse transcription–quantitative polymerase chain reaction (RT-qPCR). A total of 54 tissue samples from HBV-infected individuals were collected, genotyped, and categorized into three groups; AA (n = 32), AG (n = 18), and GG (n = 4). The expression levels of gene PDCD1 and its corresponding PD-1 protein were significantly declined in the AA group as compared to AG and GG groups. There was a negative linear association between PDCD1 and miR-4717 in the tissue samples. HEPG2 cells transfected with an miR-4717 mimic or PD-1 small interfering (si)RNA exhibited significantly reduced expression levels of PDCD1 and PD-1, whereas cells transfected with an inhibitor of miR-4717 demonstrated greater expression levels of PDCD1 and PD-1 compared with the scramble control. In addition, cell viability and apoptosis were assessed in cells transfected with an miR-4717 mimic, PD-1 siRNA, or an miR-4717 inhibitor. Results revealed that treatment with the miR-4717 mimic or PD-1 siRNA enhanced viability of cells and reduced apoptosis. The results of this study suggest that rs10204525 polymorphism interferes with the interaction between PD-1 and miR-4717 and therefore induces apoptosis in liver cancer cells.

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The role of the I/D polymorphism in the angiotensin-converting enzyme gene in selected cardiovascular diseases

Postępy Higieny i Medycyny Doświadczalnej ◽

10.5604/01.3001.0012.2427 ◽

2018 ◽

Vol 72 ◽

pp. 760-766

Author(s):

Justyna Kamińska ◽

Aneta Leszczyńska ◽

Kamil Bujak ◽

Bożena Szyguła-Jurkiewicz

Keyword(s):

Cardiovascular Diseases ◽

Angiotensin Converting Enzyme ◽

Current Knowledge ◽

Nucleotide Polymorphisms ◽

Converting Enzyme ◽

Single Nucleotide ◽

Ace Activity ◽

Artery Disease ◽

Genetically Determined

Angiotensin converting enzyme (ACE) plays an essential role in the functioning of two important systems in the human body by catalysing the synthesis of angiotensin II in the renin-angiotensin-aldosterone system and by degrading bradykinin in the kinin-kallikrein involved in the development of many cardiovascular conditions. It has been shown that ACE activity is largely genetically determined. More than nine hundred various polymorphisms, mostly single nucleotide polymorphisms, have been detected in the ACE gene; however, the most researched one is still the insertion/deletion polymorphism located in intron 16, which determines fifty per cent of variability of ACE activity. It is stated that DD homozygotes have the highest ACE serum activity, which can indicate a higher risk of developing certain cardiovascular diseases in patients with this genotype. Therefore, the I/D polymorphism has been analysed in thousands of studies, mainly in the context of cardiovascular conditions risk. The correlation between ACE I/D polymorphism and the risk of particular diseases, its cooperation with other risk factors or its influence on therapy among patients with conditions such as coronary artery disease, hypertension, atrial fibrillation and heart failure have been searched. Unfortunately, the results of those studies have often turned out ambiguous or even contrary. We herein present a summary of the most essential analyses and current knowledge about the role of the I/D polymorphism in the evaluation of risk and treatment efficacy of most common cardiovascular conditions.

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HLA RNA Sequencing With Unique Molecular Identifiers Reveals High Allele-Specific Variability in mRNA Expression

Frontiers in Immunology ◽

10.3389/fimmu.2021.629059 ◽

2021 ◽

Vol 12 ◽

Author(s):

Tiira Johansson ◽

Dawit A. Yohannes ◽

Satu Koskela ◽

Jukka Partanen ◽

Päivi Saavalainen

Keyword(s):

Mrna Expression ◽

Rna Sequencing ◽

Allelic Variation ◽

Hla Class I ◽

Sequencing Technology ◽

Hla Alleles ◽

Expression Levels ◽

Allele Specific ◽

Specific Mrna

The HLA gene complex is the most important single genetic factor in susceptibility to most diseases with autoimmune or autoinflammatory origin and in transplantation matching. Most studies have focused on the vast allelic variation in these genes; only a few studies have explored differences in the expression levels of HLA alleles. In this study, we quantified mRNA expression levels of HLA class I and II genes from peripheral blood samples of 50 healthy individuals. The gene- and allele-specific mRNA expression was assessed using unique molecular identifiers, which enabled PCR bias removal and calculation of the number of original mRNA transcripts. We identified differences in mRNA expression between different HLA genes and alleles. Our results suggest that HLA alleles are differentially expressed and these differences in expression levels are quantifiable using RNA sequencing technology. Our method provides novel insights into HLA research, and it can be applied to quantify expression differences of HLA alleles in various tissues and to evaluate the role of this type of variation in transplantation matching and susceptibility to autoimmune diseases.

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