Genetics of inclusion‐body myositis

Sporadic inclusion‐body myositis (sIBM) is the most common acquired muscle disease in Caucasians over the age of 50 years. Pathologically it is marked by inflammatory, degenerative, and mitochondrial changes that interact in a yet‐unknown way to cause progressive muscle degeneration and weakness. The cause of the disease is unknown, but it is thought to involve a complex interplay between environmental factors, genetic susceptibility, and aging. The strongest evidence for genetic susceptibility comes from studies of the major histocompatibility complex (MHC), where different combinations of alleles have been associated with sIBM in different ethnic groups. The rare occurrence of familial cases of inclusion‐body myositis (fIBM) adds additional evidence for genetic susceptibility. Other candidate genes such as those encoding some of the proteins accumulating in muscle fibers have been investigated, with negative results. The increased understanding of related disorders, the hereditary inclusion‐body myopathies (hIBM), may also provide clues to the underlying pathogenesis of sIBM, but to date there is no indication that the genes responsible for these conditions are involved in sIBM. This review summarizes current understanding of the contribution of genetic susceptibility factors to the development of sIBM. Muscle Nerve, 2007

[1]  G. Martin,et al.  Transgenic mice over-expressing the C-99 fragment of betaPP with an alpha-secretase site mutation develop a myopathy similar to human inclusion body myositis. , 1998, The American journal of pathology.

[2]  W. Engel,et al.  Strong immunoreactivity of alpha 1-antichymotrypsin co-localizes with beta-amyloid protein and ubiquitin in vacuolated muscle fibers of inclusion-body myositis. , 1993, Acta neuropathologica.

[3]  W. Engel,et al.  Abnormal accumulation of prion protein mRNA in muscle fibers of patients with sporadic inclusion-body myositis and hereditary inclusion-body myopathy. , 1994, The American journal of pathology.

[4]  W. Engel,et al.  β‐Amyloid precursor epitopes in muscle fibers of inclusion body myositis , 1993 .

[5]  K J Felice,et al.  Inclusion Body Myositis in Connecticut: Observations in 35 Patients During an 8-Year Period , 2001, Medicine.

[6]  S. Tabrizi,et al.  Sporadic inclusion body myositis not linked to prion protein codon 129 methionine homozygosity , 2000, Neurology.

[7]  A. Pestronk,et al.  Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing protein , 2004, Nature Genetics.

[8]  A. Oldfors,et al.  Inclusion Body Myositis: Clonal Expansions of Muscle‐Infiltrating T Cells Persist Over Time , 2003, Scandinavian journal of immunology.

[9]  J. Seidman,et al.  Hereditary inclusion body myopathy maps to chromosome 9p1-q1. , 1996, Human molecular genetics.

[10]  Sue Povey,et al.  Gene map of the extended human MHC , 2004, Nature Reviews Genetics.

[11]  W. Engel,et al.  New advances in inclusion-body myositis. , 1993, Current opinion in rheumatology.

[12]  N. Kasahata,et al.  [Molecular pathomechanism of distal myopathy with rimmed vacuoles]. , 2005, Rinsho shinkeigaku = Clinical neurology.

[13]  W J Litchy,et al.  Inclusion body myositis. Observations in 40 patients. , 1989, Brain : a journal of neurology.

[14]  W. Engel,et al.  Three lipoprotein receptors and cholesterol in inclusion-body myositis muscle , 2002, Neurology.

[15]  A. Roses,et al.  Apolipoprotein E alleles in sporadic inclusion‐body myositis and hereditary inclusion‐body myopathy , 1996, Annals of neurology.

[16]  M. Memo,et al.  Interleukin-1beta and glutamate activate the NF-kappaB/Rel binding site from the regulatory region of the amyloid precursor protein gene in primary neuronal cultures. , 1996, The Journal of biological chemistry.

[17]  W. Engel,et al.  Novel Immunolocalization of α‐Synuclein in Human Muscle of Inclusion‐Body Myositis, Regenerating and Necrotic Muscle Fibers, and at Neuromuscular Junctions , 2000, Journal of neuropathology and experimental neurology.

[18]  L. Kunkel,et al.  Molecular profiles of inflammatory myopathies , 2002, Neurology.

[19]  I Ferrer,et al.  Involvement of Clusterin and the Aggresome in Abnormal Protein Deposits in Myofibrillar Myopathies and Inclusion Body Myositis , 2005, Brain pathology.

[20]  S. Love,et al.  Apolipoprotein E allele frequencies in sporadic inclusion body myositis , 1996, Muscle & nerve.

[21]  M. Memo,et al.  Identification and Characterization of a κB/Rel Binding Site in the Regulatory Region of the Amyloid Precursor Protein Gene (*) , 1995, The Journal of Biological Chemistry.

[22]  E. Holme,et al.  Mitochondrial DNA Deletions in Muscle Fibers in Inclusion Body Myositis , 1995, Journal of neuropathology and experimental neurology.

[23]  V. Askanas,et al.  Unfolding Story of Inclusion-Body Myositis and Myopathies: Role of Misfolded Proteins, Amyloid-β, Cholesterol, and Aging , 2003, Journal of child neurology.

[24]  J. Piette,et al.  Familial inflammatory inclusion body myositis , 2005, Annals of the rheumatic diseases.

[25]  J. Nagle,et al.  Exons 16 and 17 of the amyloid precursor protein gene in familial inclusion body myopathy , 1995, Annals of neurology.

[26]  Baziel G M van Engelen,et al.  Inclusion body myositis. Clinical features and clinical course of the disease in 64 patients. , 2005, Journal of neurology.

[27]  F L Mastaglia,et al.  Prevalence of sporadic inclusion body myositis in Western Australia , 2000, Muscle & nerve.

[28]  A. Kaminska,et al.  Familial inclusion body myopathy with desmin storage , 1999, Acta Neuropathologica.

[29]  W. Gahl,et al.  Single nucleotide polymorphisms in the dystroglycan gene do not correlate with disease severity in hereditary inclusion body myopathy. , 2005, Molecular genetics and metabolism.

[30]  A. Kimura,et al.  Association of clinical manifestations with HLA-B alleles in Takayasu arteritis. , 1998, International journal of cardiology.

[31]  F. Zimprich,et al.  Inclusion body myopathy and Paget disease is linked to a novel mutation in the VCP gene , 2005, Neurology.

[32]  S. DeKosky,et al.  APOE*4-associated Alzheimer's disease risk is modified by alpha 1-antichymotrypsin polymorphism. , 1995, Nature genetics.

[33]  J. Malley,et al.  Differences in idiopathic inflammatory myopathy phenotypes and genotypes between Mesoamerican Mestizos and North American Caucasians: ethnogeographic influences in the genetics and clinical expression of myositis. , 2002, Arthritis and rheumatism.

[34]  J. Mendell,et al.  Mutations spectrum of GNE in hereditary inclusion body myopathy sparing the quadriceps , 2003, Human mutation.

[35]  R. Kuzniecky,et al.  Familial myopathy with changes resembling inclusion body myositis and periventricular leucoencephalopathy. A new syndrome. , 1988, Brain : a journal of neurology.

[36]  W. Engel,et al.  beta-Amyloid precursor protein mRNA is increased in inclusion-body myositis muscle. , 1993, Neuroreport.

[37]  A Seller,et al.  Normal in vivo skeletal muscle oxidative metabolism in sporadic inclusion body myositis assessed by 31P-magnetic resonance spectroscopy. , 1998, Brain : a journal of neurology.

[38]  M. Carrington,et al.  Immunogenetic Risk and Protective Factors for the Idiopathic Inflammatory Myopathies: Distinct HLA-A, -B, -Cw, -DRB1 and -DQA1 Allelic Profiles and Motifs Define Clinicopathologic Groups in Caucasians , 2005, Medicine.

[39]  Davide Pareyson,et al.  Partial laminin α2 chain deficiency in a patient with myopathy resembling inclusion body myositis , 2000 .

[40]  J R Lindsey,et al.  Amyloid-beta deposition in skeletal muscle of transgenic mice: possible model of inclusion body myopathy. , 1998, The American journal of pathology.

[41]  N. Darín,et al.  Autosomal dominant myopathy: missense mutation (Glu-706 --> Lys) in the myosin heavy chain IIa gene. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[42]  Gopal Thinakaran,et al.  Amyloidogenic processing of β-amyloid precursor protein in intracellular compartments , 2006, Neurology.

[43]  F L Mastaglia,et al.  HLA associations with inclusion body myositis , 1994, Clinical and experimental immunology.

[44]  Charles R. Harringtonaa,et al.  Apolipoprotein E type ϵ4 allele frequency is not increased in patients with sporadic inclusion-body myositis , 1995, Neuroscience Letters.

[45]  George M. Martin,et al.  Transgenic Mice Over-Expressing the C-99 Fragment of βPP with an α-Secretase Site Mutation Develop a Myopathy Similar to Human Inclusion Body Myositis , 1998 .

[46]  M. Dalakas,et al.  GNE mutations in an American family with quadriceps-sparing IBM and lack of mutations in s-IBM , 2002, Neurology.

[47]  M. Dalakas,et al.  Sporadic inclusion body myositis—diagnosis, pathogenesis and therapeutic strategies , 2006, Nature Clinical Practice Neurology.

[48]  H. Reichmann,et al.  Prion codon 129 homozygosity and sporadic inclusion body myositis , 2001, Neurology.

[49]  W. Engel,et al.  Prion protein is abnormally accumulated in inclusion‐body myositis , 1993, Neuroreport.

[50]  M. Dalakas,et al.  Absence of upregulated genes associated with protein accumulations in desmin myopathy , 2007, Muscle & nerve.

[51]  A. Kimura,et al.  Comprehensive analysis of HLA genes in Takayasu arteritis in Japan. , 1996, International journal of cardiology.

[52]  Isidro Ferrer,et al.  Proteasomal Expression, Induction of Immunoproteasome Subunits, and Local MHC Class I Presentation in Myofibrillar Myopathy and Inclusion Body Myositis , 2004, Journal of neuropathology and experimental neurology.

[53]  E. Schleicher,et al.  The RAGE pathway in inflammatory myopathies and limb girdle muscular dystrophy , 2005, Acta Neuropathologica.

[54]  J. Vance,et al.  The Deacetylase HDAC6 Regulates Aggresome Formation and Cell Viability in Response to Misfolded Protein Stress , 2003, Cell.

[55]  Tsviya Olender,et al.  The UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase gene is mutated in recessive hereditary inclusion body myopathy , 2001, Nature Genetics.

[56]  M. Dalakas,et al.  Molecular immunology and genetics of inflammatory muscle diseases. , 1998, Archives of neurology.

[57]  E. Shoubridge,et al.  Characterization of the mitochondrial DNA abnormalities in the skeletal muscle of patients with inclusion body myositis. , 1998, Journal of neuropathology and experimental neurology.

[58]  N. Niikawa,et al.  Nonaka myopathy is caused by mutations in the UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase gene (GNE) , 2002, Journal of Human Genetics.

[59]  C. Witt,et al.  Mapping of a candidate region for susceptibility to inclusion body myositis in the human major histocompatibility complex , 1999, Immunogenetics.

[60]  W. Engel,et al.  Strong immunoreactivity of α1 co-localizes with β-amyloid protein and ubiquitin in vacuolated muscle fibers of inclusion-body myositis , 2004, Acta Neuropathologica.

[61]  C. L. Jackson,et al.  Fine-structure mapping of the hereditary inclusion body myopathy locus. , 1999, Genomics.

[62]  S. Kikuchi,et al.  GNE mutations causing distal myopathy with rimmed vacuoles with inflammation , 2003, Neurology.

[63]  D. Selkoe,et al.  Twisted tubulofilaments of inclusion body myositis muscle resemble paired helical filaments of Alzheimer brain and contain hyperphosphorylated tau. , 1994, The American journal of pathology.

[64]  W. Engel,et al.  βAPP gene transfer into cultured human muscle induces inclusion‐body myositis aspects , 1997 .

[65]  M. Trucco,et al.  Altered CYP21 genes in HLA-haplotypes associated with congenital adrenal hyperplasia (CAH): a family study , 1993, Human Genetics.

[66]  A. Yu,et al.  Bcl-2, Bcl-x, and Bax expression by immunohistochemistry in inclusion body myositis: a study of 27 cases. , 2001, Archives of pathology & laboratory medicine.

[67]  G. Kollberg,et al.  Mitochondrial abnormalities in inclusion-body myositis , 2006, Neurology.

[68]  W. Engel,et al.  beta-Amyloid precursor epitopes in muscle fibers of inclusion body myositis. , 1993, Annals of neurology.

[69]  W. Engel,et al.  Immunocytochemical localization of ubiquitin in inclusion body myositis allows its light‐microscopic distinction from polymyositis , 1992, Neurology.

[70]  M. Dalakas,et al.  The spectrum of familial inclusion body myopathies in 13 families and a description of a quadriceps-sparing phenotype in non-Iranian Jews , 1996, Neurology.

[71]  Susan Walters,et al.  Familial inclusion body myositis in a mother and son with different ancestral MHC haplotypes , 2006, Neuromuscular Disorders.

[72]  F. Mastaglia,et al.  Two major histocompatibility complex haplotypes influence susceptibility to sporadic inclusion body myositis: critical evaluation of an association with HLA-DR3. , 2004, Tissue antigens.

[73]  W. Engel,et al.  Inclusion‐Body Myositis: Newest Concepts of Pathogenesis and Relation to Aging and Alzheimer Disease , 2001, Journal of neuropathology and experimental neurology.

[74]  F L Mastaglia,et al.  Apolipoprotein E ϵ4 in inclusion body myositis , 1995 .

[75]  B. V. van Engelen,et al.  Familial inclusion body myositis with histologically confirmed sensorimotor axonal neuropathy , 2000, Journal of Neurology.

[76]  Wolfgang Müller-Felber,et al.  A novel homozygous missense mutation in the GNE gene of a patient with quadriceps-sparing hereditary inclusion body myopathy associated with muscle inflammation , 2003, Neuromuscular Disorders.

[77]  X. Chen,et al.  RAGE and amyloid-β peptide neurotoxicity in Alzheimer's disease , 1996, Nature.

[78]  H. Reichmann,et al.  Apolipoprotein E and Alpha-1-Antichymotrypsin Polymorphisms in Sporadic Inclusion Body Myositis , 2004, European Neurology.

[79]  D. Darvish.  Magnesium may help patients with recessive hereditary inclusion body myopathy, a pathological review. , 2003, Medical hypotheses.

[80]  Mark A. Levenstien,et al.  Clinical delineation and localization to chromosome 9p13.3-p12 of a unique dominant disorder in four families: hereditary inclusion body myopathy, Paget disease of bone, and frontotemporal dementia. , 2001, Molecular genetics and metabolism.

[81]  S. Krause,et al.  Influence of UDP-GlcNAc 2-epimerase/ManNAc kinase mutant proteins on hereditary inclusion body myopathy. , 2006, Biochemistry.

[82]  C. Harrington,et al.  Apolipoprotein E type epsilon 4 allele frequency is not increased in patients with sporadic inclusion-body myositis. , 1995, Neuroscience letters.

[83]  M. Memo,et al.  Interleukin-1β and Glutamate Activate the NF-κB/Rel Binding Site from the Regulatory Region of the Amyloid Precursor Protein Gene in Primary Neuronal Cultures* , 1996, The Journal of Biological Chemistry.

[84]  M. Ilyas Kamboh,et al.  A4POE*4-associated Alzheimer's disease risk is modified by α1–antichymotrypsin polymorphism , 1995, Nature Genetics.

[85]  M. Dalakas,et al.  A New Approach to the Classification of Idiopathic Inflammatory Myopathy: Myositis‐Specific Autoantibodies Define Useful Homogeneous Patient Groups , 1991, Medicine.

[86]  S. Sorbi,et al.  Implication of α1-antichymotrypsin polymorphism in familial Alzheimer's disease , 1998, Neuroscience Letters.

[87]  M. Dalakas,et al.  Gene expression profile in the muscles of patients with inflammatory myopathies: effect of therapy with IVIg and biological validation of clinically relevant genes. , 2005, Brain : a journal of neurology.

[88]  R. Hohlfeld,et al.  Constitutive and cytokine-induced expression of human leukocyte antigens and cell adhesion molecules by human myotubes. , 1993, The American journal of pathology.

[89]  Y. Pouliot,et al.  Expression of immunoreactive major histocompatibility complex products in human skeletal muscles , 1988, Annals of neurology.

[90]  R. Wada,et al.  Conditional up-regulation of MHC class I in skeletal muscle leads to self-sustaining autoimmune myositis and myositis-specific autoantibodies. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[91]  Z. Argov,et al.  “Rimmed vacuole myopathy” sparing the quadriceps A unique disorder in iranian jews , 1984, Journal of the Neurological Sciences.

[92]  I. Hausmanowa-Petrusewicz,et al.  Coexistence of X-linked recessive Emery-Dreifuss muscular dystrophy with inclusion body myositis-like morphology , 2004, Acta Neuropathologica.

[93]  M. Dalakas,et al.  Inclusion body myositis and myopathies , 1997, Journal of the Neurological Sciences.

[94]  B. Hernández-Charro,et al.  El polimorfismo ACT/AA podría duplicar el riesgo de enfermedad de Alzheimer asociado al alelo APOE*ε4 , 2004 .

[95]  W. Engel,et al.  Inclusion-body myositis , 2006, Neurology.

[96]  S. Mitrani‐Rosenbaum,et al.  Various types of herediary inclusion body myopathies map to chromosome 9p1‐q1 , 1997, Annals of neurology.

[97]  R. Ellis,et al.  Medicine: Danger — misfolding proteins , 2002, Nature.

[98]  G. Gronseth,et al.  Inclusion body myositis: Clinical and pathological boundaries , 1996, Annals of neurology.

[99]  F. Breedveld,et al.  Epidemiology of inclusion body myositis in the Netherlands: A nationwide study , 2000, Neurology.

[100]  Kenneth M. Rosen,et al.  β-Amyloid Peptide Expression Is Sufficient for Myotube Death: Implications for Human Inclusion Body Myopathy , 2001, Molecular and Cellular Neuroscience.

[101]  G. Serratrice,et al.  [Inclusion body myositis and neuromuscular diseases with rimmed vacuoles]. , 1992, Revue neurologique.

[102]  Marinos C. Dalakas,et al.  Rimmed vacuoles with β-amyloid and ubiquitinated filamentous deposits in the muscles of patients with long-standing denervation (postpoliomyelitis muscular atrophy): similarities with inclusion body myositis , 1998 .

[103]  L. K. Baker,et al.  Oligomeric and Fibrillar Species of Amyloid-β Peptides Differentially Affect Neuronal Viability* , 2002, The Journal of Biological Chemistry.

[104]  H. Inoko,et al.  Analysis of genes within the HLA region affecting susceptibility to ulcerative colitis. , 1993, Human immunology.

[105]  J. Verschuuren,et al.  Associations with autoimmune disorders and HLA class I and II antigens in inclusion body myositis , 2004, Neurology.

[106]  F L Mastaglia,et al.  Patterns of muscle involvement in inclusion body myositis: Clinical and magnetic resonance imaging study , 2001, Muscle & nerve.

[107]  M. Naumann,et al.  Inclusion body myositis in twins. , 1999, Neurology.

[108]  Hagen H. Kitzler,et al.  Methionine homozygosity at prion gene codon 129 may predispose to sporadic inclusion-body myositis , 1999, The Lancet.

[109]  W. Engel,et al.  Molecular pathology and pathogenesis of inclusion‐body myositis , 2005, Microscopy research and technique.

[110]  A. Schmidt,et al.  RAGE and amyloid-beta peptide neurotoxicity in Alzheimer's disease. , 1996, Nature.

[111]  Yasuto Itoyama,et al.  Familial inclusion body myositis: a report on two Japanese sisters. , 2003, Internal medicine.

[112]  Rolf Schröder,et al.  Analysis of HLA class I and II alleles in sporadic inclusion-body myositis , 2003, Journal of Neurology.

[113]  P. Tonali,et al.  α-Dystroglycan does not play a major pathogenic role in autosomal recessive hereditary inclusion-body myopathy , 2005, Neuromuscular Disorders.

[114]  Salvatore Monaco,et al.  Increased Expression of the Normal Cellular Isoform of Prion Protein in Inclusion‐Body Myositis, Inflammatory Myopathies and Denervation Atrophy , 2001, Brain pathology.

[115]  K. Weisgraber,et al.  Apolipoprotein E and apolipoprotein E messenger RNA in muscle of inclusion body myositis and myopathies , 1996, Annals of neurology.

[116]  F. Christiansen,et al.  The genetic basis for the association of the 8.1 ancestral haplotype (A1, B8, DR3) with multiple immunopathological diseases , 1999, Immunological reviews.

[117]  F. Mastaglia,et al.  Sporadic inclusion body myositis in Japanese is associated with the MHC ancestral haplotype 52.1 , 2006, Neuromuscular Disorders.

[118]  M. Dalakas,et al.  HLA allele distribution distinguishes sporadic inclusion body myositis from hereditary inclusion body myopathies , 1998, Journal of Neuroimmunology.

[119]  W. Engel,et al.  Light and electron microscopic immunolocalization of presenilin 1 in abnormal muscle fibers of patients with sporadic inclusion-body myositis and autosomal-recessive inclusion-body myopathy. , 1998, The American journal of pathology.

[120]  N. Darín,et al.  Dominant hereditary inclusion-body myopathy gene (IBM3) maps to chromosome region 17p13.1. , 1999, American journal of human genetics.

[121]  F. Mastaglia,et al.  Mitochondrial DNA variants in inclusion body myositis , 2000, Neuromuscular Disorders.

[122]  E. Hoffman,et al.  Activation of the endoplasmic reticulum stress response in autoimmune myositis: potential role in muscle fiber damage and dysfunction. , 2005, Arthritis and rheumatism.

[123]  N. Darín,et al.  Autosomal dominant myopathy with congenital joint contractures, ophthalmoplegia, and rimmed vacuoles , 1998, Annals of neurology.

[124]  D. Arnold,et al.  Intracellular phosphates in inclusion body myositis—A 31P magnetic resonance spectroscopy study , 1998 .

[125]  M. Dalakas,et al.  An inflammatory, familial, inclusion body myositis with autoimmune features and a phenotype identical to sporadic inclusion body myositis. Studies in three families. , 1997, Brain : a journal of neurology.

[126]  H. W. Harris,et al.  Interleukin 1 regulates synthesis of amyloid beta-protein precursor mRNA in human endothelial cells. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[127]  F. Christiansen,et al.  Ancestral haplotypes: conserved population MHC haplotypes. , 1992, Human immunology.

[128]  R. Bedlack,et al.  Apolipoprotein E and neuromuscular disease: a critical review of the literature. , 2000, Archives of neurology.