title: Genetic basis of myasthenia gravis - a comprehensive review.
abstract: Myasthenia gravis (MG) is a rare autoimmune disease characterized by the production of autoantibodies against proteins of the postsynaptic membrane in the neuromuscular junction. The estimated number of MG patients is steadily increasing, and it had more than doubled in the last 20 years. Monozygotic MG twin concordance is estimated to be about 35% supporting the central role of environmental factors in MG etiology. Epigenetics, presume to be the mechanistic link between environmental and genetic risk factors in disease development, provides support for specific microRNAs associated with MG. Genetic studies have mainly pointed at specific HLA alleles implicated in MG susceptibility, however recently both TNFAIP3-interacting protein 1 (TNIP1) and tyrosine phosphatase non-receptor 22 (PTPN22) were indicated to be associated with MG in a GWAS study. A gender bias was observed for SNPs in the HLA-locus, suggesting female-specific alleles have an increase risk for MG. Moreover, sex hormones play a pivotal role in the gender bias in autoimmunity in general and in MG in particular. Hence the genetic basis of gender bias might be highly pertinent to MG and deserves further characterization. Pathway-based analyses that combine information across multiple genes into a limited number of molecular networks have been found to be a powerful approach. Both regulatory T-cell (Treg) differentiation and NF-κB signaling pathway have been shown to have relevance to MG pathophysiology. Hence studies centered around two pathways might be a fruitful approach to identify additional polymorphisms associated with myasthenia gravis.
authors.affiliation: Pharmacogenetics and Translational Genetics Center, Rappaport Faculty of Medicine & Research Institute, Technion-Israel Institute of Technology, Efron 1, Haifa 31096, Israel. Electronic address: navidan@tx.technion.ac.il.
authors.forename: Nili
authors.initials: N
authors.lastname: Avidan
authors.affiliation: INSERM U974, CNRS UMR 7215, UPMC Univ Paris 6, AIM-Institute of Myology, Paris, France.
authors.forename: Rozen
authors.initials: R
authors.lastname: Le Panse
authors.affiliation: INSERM U974, CNRS UMR 7215, UPMC Univ Paris 6, AIM-Institute of Myology, Paris, France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Berrih-Aknin
authors.affiliation: Pharmacogenetics and Translational Genetics Center, Rappaport Faculty of Medicine & Research Institute, Technion-Israel Institute of Technology, Efron 1, Haifa 31096, Israel; Division of Neuroimmunology and Multiple Sclerosis Center, Carmel Medical Center, Haifa, Israel.
authors.forename: Ariel
authors.initials: A
authors.lastname: Miller
mesh_terms: D002454:Cell Differentiation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D044127:Epigenesis, Genetic; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D009157:Myasthenia Gravis / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism; D011110:Polymorphism, Genetic; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics*; D012737:Sex Factors; D015398:Signal Transduction / Q000235:genetics; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D004268:DNA-Binding Proteins; D006680:HLA Antigens; D016328:NF-kappa B; C117046:TNIP1 protein, human; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22
keywords: Epigenetic; Gender; Genetics; Myasthenia gravis; NF-κB signaling pathway; TNIP1