title: Recent advances in genetic predisposition of myasthenia gravis.
abstract: Myasthenia gravis (MG) is an autoimmune disease mediated by the presence of autoantibodies that bind to components of the neuromuscular junction, causing the symptoms of muscular weakness and fatigability. Like most autoimmune disorders, MG is a multifactorial, noninherited disease, though with an established genetic constituent. The heterogeneity observed in MG perplexes genetic analysis even more, as it occurs in various levels, including diverse autoantigens, thymus histopathology, and age at onset. In this context of distinct subgroups, a plethora of association studies, discussed in this review, have assessed the involvement of various HLA and non-HLA related loci in MG susceptibility, over the past five years. As expected, certain HLA alleles were strongly associated with MG. Many of the non-HLA genes, such as PTPN22 and CTLA-4, have been previously studied in MG and other autoimmune diseases and their association with MG has been reevaluated in more cohesive groups of patients. Moreover, novel risk or protective loci have been revealed, as in the case of TNIP1 and FOXP3. Although the majority of these results have been derived from candidate gene studies, the focal point of all recent genetic studies is the first genome-wide association study (GWAS) conducted on early-onset MG patients.
authors.affiliation: Laboratory of Molecular Biology and Immunology, Department of Pharmacy, School of Health Sciences, University of Patras, 26504 Rio, Patras, Greece.
authors.forename: Zoi
authors.initials: Z
authors.lastname: Zagoriti
authors.forename: Manousos E
authors.initials: ME
authors.lastname: Kambouris
authors.forename: George P
authors.initials: GP
authors.lastname: Patrinos
authors.forename: Socrates J
authors.initials: SJ
authors.lastname: Tzartos
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Poulas
mesh_terms: D017668:Age of Onset; D000483:Alleles; D004268:DNA-Binding Proteins / Q000235:genetics; D051858:Forkhead Transcription Factors / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D009157:Myasthenia Gravis / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C117046:TNIP1 protein, human; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22