title: Two major histocompatibility complex haplotypes influence susceptibility to sporadic inclusion body myositis: critical evaluation of an association with HLA-DR3.
abstract: Previous studies of sporadic inclusion body myositis (sIBM) have shown a strong association with HLA-DR3 and other components of the 8.1 ancestral haplotype (AH) (HLA-A1, B8, DR3), where the susceptibility locus has been mapped to the central major histocompatibility complex (MHC) region between HLA-DR and C4. Here, the association with HLA-DR3 and other genes in the central MHC and class II region was further investigated in a group of 42 sIBM patients and in an ethnically similar control group (n = 214), using single-nucleotide polymorphisms and microsatellite screening. HLA-DR3 (marking DRB1*0301 in Caucasians) was associated with sIBM (Fisher's test). However, among HLA-DR3-positive patients and controls, carriage of HLA-DR3 without microsatellite and single-nucleotide polymorphism alleles of the 8.1AH (HLA-A1, B8, DRB3*0101, DRB1*0301, DQB1*0201) was marginally less common in patients. Patients showed no increase in carriage of the 18.2AH (HLA-A30, B18, DRB3*0202, DRB1*0301, DQB1*0201) or HLA-DR3 without the central MHC of the 8.1AH, further arguing against HLA-DRB1 as the direct cause of susceptibility. Genes between HLA-DRB1 and HOX12 require further investigation. BTL-II lies in this region and is expressed in muscle. Carriage of allele 2 (exon 6) was more common in patients. BTL-II(E6)*2 is characteristic of the 35.2AH (HLA-A3, B35, DRB1*01) in Caucasians and HLA-DR1, BTL-II(E6)*2, HOX12*2, RAGE*2 was carried by several patients. The 8.1AH and 35.2AH may confer susceptibility to sIBM independently or share a critical allele.
authors.affiliation: School of Surgery and Pathology, University of Western Australia, Nedlands, Australia. pprice@cyllene.uwa.edu.au
authors.forename: P
authors.initials: P
authors.lastname: Price
authors.forename: L
authors.initials: L
authors.lastname: Santoso
authors.forename: F
authors.initials: F
authors.lastname: Mastaglia
authors.forename: M
authors.initials: M
authors.lastname: Garlepp
authors.forename: C C
authors.initials: CC
authors.lastname: Kok
authors.forename: R
authors.initials: R
authors.lastname: Allcock
authors.forename: N
authors.initials: N
authors.lastname: Laing
mesh_terms: D000071797:Butyrophilins; D020022:Genetic Predisposition to Disease; D015795:HLA-B8 Antigen / Q000235:genetics / Q000276:immunology; D015803:HLA-DR3 Antigen / Q000235:genetics* / Q000276:immunology; D006239:Haplotypes / Q000235:genetics / Q000276:immunology; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics* / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D018979:Myositis, Inclusion Body / Q000235:genetics* / Q000276:immunology
chemical_list: C408263:BTNL2 protein, human; D000071797:Butyrophilins; D015795:HLA-B8 Antigen; D015803:HLA-DR3 Antigen; D008562:Membrane Glycoproteins