ArticleJournal of neuroinflammation2018
Exome sequencing study in patients with multiple sclerosis reveals variants associated with disease course.
Article in Journal of neuroinflammation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 34 citations in OpenAlex.
- Genetic Prognostic Factors in Multiple Sclerosis: Key Discoveries and Unmet Needs.International journal of molecular sciences · 2026Review
- Neuroanatomical characterization of the cell adhesion molecule IgSF9b reveals localization to inhibitory and excitatory synapses in the mouse limbic system.Journal of molecular medicine (Berlin, Germany) · 2025Article
- Molecular mechanisms and regulation of inflammasome activation and signaling: sensing of pathogens and damage molecular patterns.Cellular & molecular immunology · 2025Review
- Pattern Recognition by NOD-Like Receptors.Advances in experimental medicine and biology · 2025Review
- Molecular mechanisms of emerging inflammasome complexes and their activation and signaling in inflammation and pyroptosis.Immunological reviews · 2025Review
- NLRP inflammasomes in health and disease.Molecular biomedicine · 2024Review
- The role of cell adhesion molecule IgSF9b at the inhibitory synapse and psychiatric disease.Neuroscience and biobehavioral reviews · 2024Review
- Inactive metallopeptidase homologs: the secret lives of pseudopeptidases.Frontiers in molecular biosciences · 2024Review
- Methyl-CpG-Binding Protein 2 Emerges as a Central Player in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders.Cellular and molecular neurobiology · 2023Review
- In silico analysis and molecular docking studies of natural compounds of Withania somnifera against bovine NLRP9.Journal of molecular modeling · 2023Article
- The regulation of self-tolerance and the role of inflammasome molecules.Frontiers in immunology · 2023Review
- Insights into inflammasome regulation: cellular, molecular, and pathogenic control of inflammasome activation.Immunologic research · 2022Review
- Genetics behind Cerebral Disease with Ocular Comorbidity: Finding Parallels between the Brain and Eye Molecular Pathology.International journal of molecular sciences · 2022Review
- Epigenome-Wide Analysis Reveals DNA Methylation Alteration inChildren (Basel, Switzerland) · 2022Article
- Cpxm2 as a novel candidate for cardiac hypertrophy and failure in hypertension.Hypertension research : official journal of the Japanese Society of Hypertension · 2022Article
- Liver kinase B1 rs9282860 polymorphism and risk for multiple sclerosis in White and Black Americans.Multiple sclerosis and related disorders · 2021Article
- NLRP9 in innate immunity and inflammation.Immunology · 2021Review
- Genomic, proteomic, and systems biology approaches in biomarker discovery for multiple sclerosis.Cellular immunology · 2020Review
- Article
- Genetic analysis of nucleotide-binding leucine-rich repeat (NLR) receptors in multiple sclerosis.Immunogenetics · 2020Article
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Authors and funding
25 authors at 12 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIt remains unclear whether disease course in multiple sclerosis (MS) is influenced by genetic polymorphisms. Here, we aimed to identify genetic variants associated with benign and aggressive disease courses in MS patients.
methodsMS patients were classified into benign and aggressive phenotypes according to clinical criteria. We performed exome sequencing in a discovery cohort, which included 20 MS patients, 10 with benign and 10 with aggressive disease course, and genotyping in 2 independent validation cohorts. The first validation cohort encompassed 194 MS patients, 107 with benign and 87 with aggressive phenotypes. The second validation cohort comprised 257 patients, of whom 224 patients had benign phenotypes and 33 aggressive disease courses. Brain immunohistochemistries were performed using disease course associated genes antibodies.
resultsBy means of single-nucleotide polymorphism (SNP) detection and comparison of allele frequencies between patients with benign and aggressive phenotypes, a total of 16 SNPs were selected for validation from the exome sequencing data in the discovery cohort. Meta-analysis of genotyping results in two validation cohorts revealed two polymorphisms, rs28469012 and rs10894768, significantly associated with disease course. SNP rs28469012 is located in CPXM2 (carboxypeptidase X, M14 family, member 2) and was associated with aggressive disease course (uncorrected p value < 0.05). SNP rs10894768, which is positioned in IGSF9B (immunoglobulin superfamily member 9B) was associated with benign phenotype (uncorrected p value < 0.05). In addition, a trend for association with benign phenotype was observed for a third SNP, rs10423927, in NLRP9 (NLR family pyrin domain containing 9). Brain immunohistochemistries in chronic active lesions from MS patients revealed expression of IGSF9B in astrocytes and macrophages/microglial cells, and expression of CPXM2 and NLRP9 restricted to brain macrophages/microglia.
conclusionsGenetic variants located in CPXM2, IGSF9B, and NLRP9 have the potential to modulate disease course in MS patients and may be used as disease activity biomarkers to identify patients with divergent disease courses. Altogether, the reported results from this study support the influence of genetic factors in MS disease course and may help to better understand the complex molecular mechanisms underlying disease pathogenesis.
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