ArticleGenes and immunity2010
A functional SNP in the regulatory region of the decay-accelerating factor gene associates with extraocular muscle pareses in myasthenia gravis.
Article in Genes and immunity, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 38 citations in OpenAlex.
- The Epidemiology and Phenotypes of Ocular Manifestations in Childhood and Juvenile Myasthenia Gravis: A Review.Frontiers in neurology · 2022Review
- Profiling of patient-specific myocytes identifies altered gene expression in the ophthalmoplegic subphenotype of myasthenia gravis.Orphanet journal of rare diseases · 2019Article
- Using Whole Genome Sequencing in an African Subphenotype of Myasthenia Gravis to Generate a Pathogenetic Hypothesis.Frontiers in genetics · 2019Article
- Homo sapiens-Specific Binding Site Variants within Brain Exclusive Enhancers Are Subject to Accelerated Divergence across Human Population.Genome biology and evolution · 2018Article
- Preconditioned mesenchymal stem cells treat myasthenia gravis in a humanized preclinical model.JCI insight · 2017Article
- Semantic prioritization of novel causative genomic variants.PLoS computational biology · 2017Article
- The African-387 C>T TGFB1 variant is functional and associates with the ophthalmoplegic complication in juvenile myasthenia gravis.Journal of human genetics · 2016Article
- The role of decay accelerating factor in environmentally induced and idiopathic systemic autoimmune disease.Autoimmune diseases · 2014Review
- Implications of genomic signatures in the differential vulnerability to fetal alcohol exposure in C57BL/6 and DBA/2 mice.Frontiers in genetics · 2014Article
- Article
- Biomarker development for myasthenia gravis.Annals of the New York Academy of Sciences · 2012Review
- Analysis of multiple polymorphisms in the bovine neuropeptide Y5 receptor gene and structural modelling of the encoded protein.Molecular biology reports · 2012Article
- Mutations and binding sites of human transcription factors.Frontiers in genetics · 2012Article
- dPORE-miRNA: polymorphic regulation of microRNA genes.PloS one · 2011Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Complement activation in myasthenia gravis (MG) may damage muscle endplate and complement regulatory proteins such as decay-accelerating factor (DAF) or CD55 may be protective. We hypothesize that the increased prevalence of severe extraocular muscle (EOM) dysfunction among African MG subjects reported earlier may result from altered DAF expression. To test this hypothesis, we screened the DAF gene sequences relevant to the classical complement pathway and found an association between myasthenics with EOM paresis and the DAF regulatory region c.-198C>G SNP (odds ratio=8.6; P=0.0003). This single nucleotide polymorphism (SNP) results in a twofold activation of a DAF 5'-flanking region luciferase reporter transfected into three different cell lines. Direct matching of the surrounding SNP sequence within the DAF regulatory region with the known transcription factor-binding sites suggests a loss of an Sp1-binding site. This was supported by the observation that the c.-198C>G SNP did not show the normal lipopolysaccharide-induced DAF transcriptional upregulation in lymphoblasts from four patients. Our findings suggest that at critical periods during autoimmune MG, this SNP may result in inadequate DAF upregulation with consequent complement-mediated EOM damage. Susceptible individuals may benefit from anti-complement therapy in addition to immunosuppression.
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