Functional significance of the rare rs35667974 IFIH1 gene polymorphism, associated with multiple autoimmune diseases, using a structural biological approach
Autoimmune diseases, which affect approximately 5% of human population, are a range of diseases in which the immune response to self-antigens results in damage or dysfunction of tissues. Recent genome wide association studies (GWAS) have successfully identified novel autoimmune disease-associated lo...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-09-01
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| Series: | Autoimmunity |
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| Online Access: | http://dx.doi.org/10.1080/08916934.2022.2103799 |
| _version_ | 1827817278878515200 |
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| author | Maria I. Zervou Athena C. Andreou Elias E. Eliopoulos George N. Goulielmos |
| author_facet | Maria I. Zervou Athena C. Andreou Elias E. Eliopoulos George N. Goulielmos |
| author_sort | Maria I. Zervou |
| collection | DOAJ |
| description | Autoimmune diseases, which affect approximately 5% of human population, are a range of diseases in which the immune response to self-antigens results in damage or dysfunction of tissues. Recent genome wide association studies (GWAS) have successfully identified novel autoimmune disease-associated loci, with many of them shared by multiple disease-associated pathways but much of the genetics and pathophysiological mechanisms remain still obscure. Considering that most of the potential causal variants are still unknown, many studies showed that the missense variant rs35667974 at interferon-induced with helicase C domain 1 (IFIH1) gene is protective for type 1 diabetes (T1D), psoriasis (PS) and psoriatic arthritis (PsA). Recently, this variant was found to be also associated with ankylosing spondylitis (AS), Crohn’s disease (CD) and ulcerative colitis (UC). The IFIH1 gene encodes a cytoplasmic RNA helicase otherwise known as melanoma differentiation-associated 5 (MDA5) that recognizes viral RNA and is involved in innate immunity through recognition of viral RNA. In the present study we sought to investigate the association of the rare rs35667974 variant of IFIH1 gene, which resides in exon 14 and changes a conserved isoleucine at position #923 to valine, in the development of various autoimmune diseases and give a reason for the selectivity affecting different autoimmune diseases. Evolutionary studies and three-dimensional (3 D) homology modelling were employed on the MDA5 protein product, through its association with dsRNA, recognition factor controlling cytokine and chemokine signalling, to investigate the protective role of the MDA5 variant for certain autoimmune diseases. |
| first_indexed | 2024-03-12T00:32:08Z |
| format | Article |
| id | doaj.art-4fd42cdc3dbb4d5dbd038f719b4a13fc |
| institution | Directory Open Access Journal |
| issn | 0891-6934 1607-842X |
| language | English |
| last_indexed | 2024-03-12T00:32:08Z |
| publishDate | 2022-09-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Autoimmunity |
| spelling | doaj.art-4fd42cdc3dbb4d5dbd038f719b4a13fc2023-09-15T10:12:25ZengTaylor & Francis GroupAutoimmunity0891-69341607-842X2022-09-0155745546110.1080/08916934.2022.21037992103799Functional significance of the rare rs35667974 IFIH1 gene polymorphism, associated with multiple autoimmune diseases, using a structural biological approachMaria I. Zervou0Athena C. Andreou1Elias E. Eliopoulos2George N. Goulielmos3Section of Molecular Pathology and Human Genetics, Department of Internal Medicine, School of Medicine, University of CreteLaboratory of Genetics, Department of Biotechnology, Agricultural University of AthensLaboratory of Genetics, Department of Biotechnology, Agricultural University of AthensSection of Molecular Pathology and Human Genetics, Department of Internal Medicine, School of Medicine, University of CreteAutoimmune diseases, which affect approximately 5% of human population, are a range of diseases in which the immune response to self-antigens results in damage or dysfunction of tissues. Recent genome wide association studies (GWAS) have successfully identified novel autoimmune disease-associated loci, with many of them shared by multiple disease-associated pathways but much of the genetics and pathophysiological mechanisms remain still obscure. Considering that most of the potential causal variants are still unknown, many studies showed that the missense variant rs35667974 at interferon-induced with helicase C domain 1 (IFIH1) gene is protective for type 1 diabetes (T1D), psoriasis (PS) and psoriatic arthritis (PsA). Recently, this variant was found to be also associated with ankylosing spondylitis (AS), Crohn’s disease (CD) and ulcerative colitis (UC). The IFIH1 gene encodes a cytoplasmic RNA helicase otherwise known as melanoma differentiation-associated 5 (MDA5) that recognizes viral RNA and is involved in innate immunity through recognition of viral RNA. In the present study we sought to investigate the association of the rare rs35667974 variant of IFIH1 gene, which resides in exon 14 and changes a conserved isoleucine at position #923 to valine, in the development of various autoimmune diseases and give a reason for the selectivity affecting different autoimmune diseases. Evolutionary studies and three-dimensional (3 D) homology modelling were employed on the MDA5 protein product, through its association with dsRNA, recognition factor controlling cytokine and chemokine signalling, to investigate the protective role of the MDA5 variant for certain autoimmune diseases.http://dx.doi.org/10.1080/08916934.2022.2103799autoimmune diseasesgene polymorphismthree-dimensional structureinterferon induced with helicase c domain 1 (ifih1)mda5 |
| spellingShingle | Maria I. Zervou Athena C. Andreou Elias E. Eliopoulos George N. Goulielmos Functional significance of the rare rs35667974 IFIH1 gene polymorphism, associated with multiple autoimmune diseases, using a structural biological approach Autoimmunity autoimmune diseases gene polymorphism three-dimensional structure interferon induced with helicase c domain 1 (ifih1) mda5 |
| title | Functional significance of the rare rs35667974 IFIH1 gene polymorphism, associated with multiple autoimmune diseases, using a structural biological approach |
| title_full | Functional significance of the rare rs35667974 IFIH1 gene polymorphism, associated with multiple autoimmune diseases, using a structural biological approach |
| title_fullStr | Functional significance of the rare rs35667974 IFIH1 gene polymorphism, associated with multiple autoimmune diseases, using a structural biological approach |
| title_full_unstemmed | Functional significance of the rare rs35667974 IFIH1 gene polymorphism, associated with multiple autoimmune diseases, using a structural biological approach |
| title_short | Functional significance of the rare rs35667974 IFIH1 gene polymorphism, associated with multiple autoimmune diseases, using a structural biological approach |
| title_sort | functional significance of the rare rs35667974 ifih1 gene polymorphism associated with multiple autoimmune diseases using a structural biological approach |
| topic | autoimmune diseases gene polymorphism three-dimensional structure interferon induced with helicase c domain 1 (ifih1) mda5 |
| url | http://dx.doi.org/10.1080/08916934.2022.2103799 |
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