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Genetic Basis of Autoimmune Diseases
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Genetic Basis of Autoimmune Diseases

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Human Genomics and Genetic Diseases".

Deadline for manuscript submissions: closed (10 August 2023) | Viewed by 10791

Special Issue Editor

Dr. Mitesh Dwivedi

E-Mail Website
Guest Editor
C. G. Bhakta Institute of Biotechnology, Faculty of Science, Uka Tarsadia University, Bardoli, Surat 394 350, Gujarat, India
Interests: immunogentics; vitiligo; autoimmunity; rheumatoid arthritis; genetic association studies

Special Issue Information

Dear Colleagues,

Autoimmune diseases are characterized by an aberrant immune response against the host's own cell and tissues, wherein the immune system loses immunological tolerance and recognizes the self as non-self. Given the fact that ~70% of human genes contributes to immune system functioning, autoimmune diseases can develop due to alterations in these immune regulatory genes. Many autoimmune diseases (organ-specific autoimmune diseases (e.g., T1DM, multiple sclerosis, Hashimoto’s thyroiditis, Vitiligo, Graves’ disease, autoimmune anemias, Goodpasture’s Syndrome, myasthenia gravis, etc.) or  systemic autoimmune diseases (e.g., rheumatoid arthritis, systemic lupus erythematosus, spondylarthropathies, systemic sclerosis, and Sjogrens syndrome, etc.)) are considered complex genetic diseases due to the involvement of mutiple genes. Exploring the genetic susceptibility factors for these autoimmune diseases will be helpful in delineating their exact roles in altering the immune pathways and can help in designing marker-assisted diagnostics, personalized therapy and possible genetic interventions for various autoimmune diseases. This Special Issue invites contributions dealing with the genetic basis of various autoimmune diseases through genetic association studies involving different strategies, ranging from linkage studies, candidate gene association studies to genome-wide association studies. In addition, review articles, genotype–phenotype correlations, gene–gene interactions and meta-analysis studies are also welcomed in this issue.

Dr. Mitesh Dwivedi
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Genes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (5 papers)

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Research

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12 pages, 2242 KiB  
Article
Statistical Mechanics Metrics in Pairing and Parsing In Silico and Phenotypic Data of a Novel Genetic NFκB1 (c.T638A) Variant
by Eman N. Chaudhri, Jessica M. Abbott, Naeyma N. Islam, Caleb A. Weber, Mathew A. Coban, Ahmet Bilgili, Jacqueline D. Squire, Sarah Mantia, Klaas J. Wierenga and Thomas R. Caulfield
Genes 2023, 14(10), 1855; https://doi.org/10.3390/genes14101855 - 24 Sep 2023
Viewed by 1397
Abstract
(1) Background: Mutations in NFκB1, a transcriptional regulator of immunomodulating proteins, are a known cause of inborn errors of immunity. Our proband is a 22-year-old male with a diagnosis of common variable immunodeficiency (CVID), cytopenias with massive splenomegaly, and nodular regenerative hyperplasia [...] Read more.
(1) Background: Mutations in NFκB1, a transcriptional regulator of immunomodulating proteins, are a known cause of inborn errors of immunity. Our proband is a 22-year-old male with a diagnosis of common variable immunodeficiency (CVID), cytopenias with massive splenomegaly, and nodular regenerative hyperplasia of the liver. Genetic studies identified a novel, single-point mutation variant in NFκB1, c. T638A p. V213E. (2) Methods: Next-generation panel sequencing of the patient uncovered a novel single-point mutation in the NFκB1 gene that was modeled using the I-TASSER homology-modeling software, and molecular dynamics were assessed using the YASARA2 software (version 20.14.24). (3) Results: This variant replaces valine with glutamic acid at position 213 in the NFκB1 sequence. Molecular modeling and molecular dynamic studies showed altered dynamics in and around the rel homology domain, ankyrin regions, and death domain of the protein. We postulate that these changes alter overall protein function. (4) Conclusions: This case suggests the pathogenicity of a novel variant using protein-modeling techniques and molecular dynamic simulations. Full article
(This article belongs to the Special Issue Genetic Basis of Autoimmune Diseases)
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12 pages, 3138 KiB  
Article
Association between Gastric Cancer and 12 Autoimmune Diseases: A Mendelian Randomization Study
by Qi Wei, Ziyu Wang, Xuanyu Liu, Haibin Liang and Lei Chen
Genes 2023, 14(10), 1844; https://doi.org/10.3390/genes14101844 - 23 Sep 2023
Viewed by 2221
Abstract
Background: Whether the positive associations of gastric cancer (GC) with autoimmune diseases are causal has always been controversial. This study aims to estimate the causal relationship between GC and 12 autoimmune diseases by means of Mendelian randomization (MR) analysis. Methods: After rigorous evaluation, [...] Read more.
Background: Whether the positive associations of gastric cancer (GC) with autoimmune diseases are causal has always been controversial. This study aims to estimate the causal relationship between GC and 12 autoimmune diseases by means of Mendelian randomization (MR) analysis. Methods: After rigorous evaluation, potential candidate single nucleotide polymorphisms (SNPs) for GC and 12 autoimmune diseases were extracted from genome-wide association study (GWAS) datasets. We performed the MR analyses using the inverse variance weighted (IVW) method as the primary approach to the analysis. Three sensitivity analysis methods were added to assess the robustness of the results. In addition, heterogeneity was measured using Cochran’s Q-value, and horizontal pleiotropy was assessed using MR-Egger regression and leave-one-out analysis. Results: The IVW result, which is the main method of analysis, shows no evidence of a causal association between GC and any autoimmune disease. The results of IVW analysis show the relationship between rheumatoid arthritis (p = 0.1389), systemic lupus erythematosus (p = 0.1122), Crohn‘s disease (p = 0.1509), multiple sclerosis (p = 0.3944), primary sclerosing cholangitis (p = 0.9022), primary biliary cirrhosis (p = 0.7776), type 1 diabetes (p = 0.9595), ulcerative colitis (p = 0.5470), eczema (p = 0.3378), asthma (p = 0.7436), celiac disease (p = 0.4032), and psoriasis (p = 0.7622) and GC susceptibility. The same result was obtained with the weighted median and the MR-egger (p > 0.05). Conclusion: Our study did not find a genetic causal relationship between susceptibility to these autoimmune diseases and GC, which suggests that unmeasured confounders (e.g., inflammatory processes) or shared genetic architecture may be responsible for the reported epidemiologic associations. Further studies of ancestral diversity are warranted to validate such causal associations. Full article
(This article belongs to the Special Issue Genetic Basis of Autoimmune Diseases)
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10 pages, 610 KiB  
Article
Association of the STAT4 Gene rs7574865 Polymorphism with IFN-γ Levels in Patients with Systemic Lupus Erythematosus
by Yussef Esparza Guerrero, Maria Luisa Vazquez Villegas, Cesar Arturo Nava Valdivia, Juan Manuel Ponce Guarneros, Edsaul Emilio Perez Guerrero, Eli Efrain Gomez Ramirez, Melissa Ramirez Villafaña, Betsabe Contreras Haro, Alejandra Martinez Hernandez, Ernesto German Cardona Muñoz, Ismael Nuño Arana, Sergio Gabriel Gallardo Moya, Alfredo Celis, Laura Gonzalez Lopez, Jorge Ivan Gamez Nava and Ana Miriam Saldaña Cruz
Genes 2023, 14(3), 537; https://doi.org/10.3390/genes14030537 - 21 Feb 2023
Viewed by 1776
Abstract
STAT4 plays an important role in disease activity in SLE patients. STAT4 particles have the capacity to activate the transcription of genes associated with the production of TH1 and Th17 lymphocytes, with a greater predominance on the production of IFN-γ and IL-17A. The [...] Read more.
STAT4 plays an important role in disease activity in SLE patients. STAT4 particles have the capacity to activate the transcription of genes associated with the production of TH1 and Th17 lymphocytes, with a greater predominance on the production of IFN-γ and IL-17A. The presence of variants in STAT4 genes has a major impact on the generation of autoimmunity. However, there are few studies evaluating the impact of these variants on the production of proinflammatory cytokines such as IFN-γ and IL-17A. Methods—A case–control study was carried out with 206 Mexican mestizo patients residing in Western Mexico with a diagnosis of SLE and a group of 80 patients without autoimmune diseases was captured to determine the cut-off point for high IFN-γ levels. In this study, SLE patients with high IFN-γ levels were considered as cases (cut-off > 15.6 pg/mL), and SLE patients with normal IFN-γ levels were considered as controls (cut-off ≤ 15.6 pg/mL). Disease activity was identified from the systemic lupus erythematosus disease activity index (SLEDAI). For the determination of levels of cytokines IFN-γ, IL-12, and IL17A, commercial ELISA kits were used. Genotyping of STAT4 rs7574865 (G > T) was performed by quantitative polymerase chain reaction (qPCR) using TaqMan probes. Results—The patients with SLE had a median age of 45 years with a range of disease duration from 4 years to 18 years; 45.6% were identified as having disease activity. In this sample, we identified a high IFN-γ prevalence of 35.4%. The levels of IFN-γ were higher in the patients with genotype TT than GG. We found that TT genotype conferred a higher risk of high IFN-γ when compared to the GG and GT genotypes. Conclusions—In this study, we identified that the polymorphic genotype TT of the STAT4 gene rs7574865 polymorphism is associated with increased levels of IFN-γ. However, its strength of association was weak, so complementary studies are needed to evaluate its impact on SLE patients. Full article
(This article belongs to the Special Issue Genetic Basis of Autoimmune Diseases)
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Review

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17 pages, 825 KiB  
Review
Genetic and Epigenetic Mechanisms of Psoriasis
by Laura Mateu-Arrom and Lluis Puig
Genes 2023, 14(8), 1619; https://doi.org/10.3390/genes14081619 - 13 Aug 2023
Cited by 5 | Viewed by 2901
Abstract
Psoriasis is a disease involving the innate and adaptative components of the immune system, and it is triggered by environmental factors in genetically susceptible individuals. However, its physiopathology is not fully understood yet. Recent technological advances, especially in genome and epigenome-wide studies, have [...] Read more.
Psoriasis is a disease involving the innate and adaptative components of the immune system, and it is triggered by environmental factors in genetically susceptible individuals. However, its physiopathology is not fully understood yet. Recent technological advances, especially in genome and epigenome-wide studies, have provided a better understanding of the genetic and epigenetic mechanisms to determine the physiopathology of psoriasis and facilitate the development of new drugs. This review intends to summarize the current evidence on genetic and epigenetic mechanisms of psoriasis. Full article
(This article belongs to the Special Issue Genetic Basis of Autoimmune Diseases)
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21 pages, 4248 KiB  
Review
Genetic Basis of Inflammatory Demyelinating Diseases of the Central Nervous System: Multiple Sclerosis and Neuromyelitis Optica Spectrum
by Genaro Gabriel Ortiz, Blanca M. G. Torres-Mendoza, Javier Ramírez-Jirano, Jazmin Marquez-Pedroza, José J. Hernández-Cruz, Mario A. Mireles-Ramirez and Erandis D. Torres-Sánchez
Genes 2023, 14(7), 1319; https://doi.org/10.3390/genes14071319 - 23 Jun 2023
Cited by 2 | Viewed by 1816
Abstract
Demyelinating diseases alter myelin or the coating surrounding most nerve fibers in the central and peripheral nervous systems. The grouping of human central nervous system demyelinating disorders today includes multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) as distinct disease categories. Each [...] Read more.
Demyelinating diseases alter myelin or the coating surrounding most nerve fibers in the central and peripheral nervous systems. The grouping of human central nervous system demyelinating disorders today includes multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) as distinct disease categories. Each disease is caused by a complex combination of genetic and environmental variables, many involving an autoimmune response. Even though these conditions are fundamentally similar, research into genetic factors, their unique clinical manifestations, and lesion pathology has helped with differential diagnosis and disease pathogenesis knowledge. This review aims to synthesize the genetic approaches that explain the differential susceptibility between these diseases, explore the overlapping clinical features, and pathological findings, discuss existing and emerging hypotheses on the etiology of demyelination, and assess recent pathogenicity studies and their implications for human demyelination. This review presents critical information from previous studies on the disease, which asks several questions to understand the gaps in research in this field. Full article
(This article belongs to the Special Issue Genetic Basis of Autoimmune Diseases)
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