title: Genetic heterogeneity within the HLA region in three distinct clinical subgroups of myasthenia gravis.
abstract: This study aims to investigate genetic susceptibility to early-onset and late-onset anti-acetylcholine receptor antibody positive myasthenia gravis (EOMG and LOMG) and anti-muscle specific kinase antibody positive MG (MuSK-MG) at genome-wide level in a single population. Using a custom-designed array and imputing additional variants and the classical HLA alleles in 398 patients, we detected distinct associations. In EOMG, rs113519545 in the HLA class I region (OR=5.71 [3.77-8.66], P=2.24×10(-16)), HLA-B*08:01 (OR=7.04 [3.95-12.52], P=3.34×10(-11)) and HLA-C*07:01 (OR=2.74 [1.97-3.81], P=2.07(-9)), in LOMG, rs111256513 in the HLA class II region (OR=2.22 [1.59-3.09], P=2.48×10(-6)) and in MuSK-MG, an intronic variant within HLA-DQB1 (rs68081734, OR=5.86, P=2.25×10(-14)) and HLA-DQB1*05:02 (OR=8.56, P=6.88×10(-13)) revealed the most significant associations for genome-wide significance. Differential genetic susceptibility within the HLA to EOMG, LOMG and MuSK-MG has been established in a population from Turkey.
authors.affiliation: Department of Physiology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey. Electronic address: gsaruhan@istanbul.edu.tr.
authors.forename: Güher
authors.initials: G
authors.lastname: Saruhan-Direskeneli
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA; Division of Health Science and Technology, Harvard Medical School, Boston, MA, USA.
authors.forename: Travis
authors.initials: T
authors.lastname: Hughes
authors.affiliation: Department of Physiology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Vuslat
authors.initials: V
authors.lastname: Yilmaz
authors.affiliation: Department of Neurology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Hacer
authors.initials: H
authors.lastname: Durmus
authors.affiliation: Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Adler
authors.affiliation: Department of Physiology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Mahdi
authors.initials: M
authors.lastname: Alahgholi-Hajibehzad
authors.affiliation: Department of Neurology, Bakirkoy Research and Training Hospital for Psychiatric and Neurological Diseases, Istanbul, Turkey.
authors.forename: Fikret
authors.initials: F
authors.lastname: Aysal
authors.affiliation: Department of Physiology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Sibel P
authors.initials: SP
authors.lastname: Yentür
authors.affiliation: Department of Neurology, Cerrahpaşa Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Mehmet Ali
authors.initials: MA
authors.lastname: Akalin
authors.affiliation: Department of Pathology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Oner
authors.initials: O
authors.lastname: Dogan
authors.affiliation: Institute of Pathology, University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Marx
authors.affiliation: Department of Neurology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Yesim
authors.initials: Y
authors.lastname: Gülsen-Parman
authors.affiliation: Department of Neurology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Piraye
authors.initials: P
authors.lastname: Oflazer
authors.affiliation: Department of Neurology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Feza
authors.initials: F
authors.lastname: Deymeer
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Amr H
authors.initials: AH
authors.lastname: Sawalha
mesh_terms: D017668:Age of Onset; D000483:Alleles; D005260:Female; D005787:Gene Frequency; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease / Q000235:genetics; D015894:Genome, Human / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology*; D015236:HLA-C Antigens / Q000235:genetics / Q000276:immunology*; D059866:HLA-DQ beta-Chains / Q000235:genetics / Q000276:immunology*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D009157:Myasthenia Gravis / Q000453:epidemiology / Q000235:genetics / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide; D020794:Receptor Protein-Tyrosine Kinases / Q000276:immunology; D011950:Receptors, Cholinergic / Q000276:immunology; D014421:Turkey / Q000453:epidemiology
chemical_list: D015235:HLA-B Antigens; D015236:HLA-C Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D011950:Receptors, Cholinergic; C095714:MUSK protein, human; D020794:Receptor Protein-Tyrosine Kinases
keywords: EOMG; Genome-wide association; LOMG; MuSK-MG; Myasthenia gravis