title: Sporadic inclusion body myositis: HLA-DRB1 allele interactions influence disease risk and clinical phenotype.
abstract: Susceptibility to sIBM is strongly associated with the HLA-DRB1*03 allele and the 8.1 MHC ancestral haplotype (HLA-A1, B8, DRB1*03) but little is known about the effects of allelic interactions at the DRB1 locus or disease-modifying effects of HLA alleles. HLA-A, B and DRB1 genotyping was performed in 80 Australian sIBM cases and the frequencies of different alleles and allele combinations were compared with those in a group of 190 healthy controls. Genotype-phenotype correlations were also investigated. Amongst carriers of the HLA-DRB1*03 allele, DRB1*03/*01 heterozygotes were over-represented in the sIBM group (p<0.003) while. DRB1*03/*04 heterozygotes were under-represented (p<0.008). The mean age-at-onset (AAO) was 6.5 years earlier in DRB1*03/*01 heterozygotes who also had more severe quadriceps muscle weakness than the rest of the cohort. The findings indicate that interactions between the HLA-DRB1*03 allele and other alleles at the DRB1 locus can influence disease susceptibility and the clinical phenotype in sIBM.
authors.affiliation: Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Australian Neuromuscular Research Institute (ANRI), Queen Elizabeth II Medical Centre, Nedlands, Perth, WA 6009, Australia. flmast@cyllene.uwa.edu.au
authors.forename: Frank L
authors.initials: FL
authors.lastname: Mastaglia
authors.forename: Merrilee
authors.initials: M
authors.lastname: Needham
authors.forename: Adrian
authors.initials: A
authors.lastname: Scott
authors.forename: Ian
authors.initials: I
authors.lastname: James
authors.forename: Paul
authors.initials: P
authors.lastname: Zilko
authors.forename: Timothy
authors.initials: T
authors.lastname: Day
authors.forename: Lynette
authors.initials: L
authors.lastname: Kiers
authors.forename: Alastair
authors.initials: A
authors.lastname: Corbett
authors.forename: Campbell S
authors.initials: CS
authors.lastname: Witt
authors.forename: Richard
authors.initials: R
authors.lastname: Allcock
authors.forename: Nigel
authors.initials: N
authors.lastname: Laing
authors.forename: Michael
authors.initials: M
authors.lastname: Garlepp
authors.forename: Frank T
authors.initials: FT
authors.lastname: Christiansen
mesh_terms: D017668:Age of Onset; D015331:Cohort Studies; D005260:Female; D056726:Genetic Association Studies / Q000379:methods; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics*; D015803:HLA-DR3 Antigen / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D018979:Myositis, Inclusion Body / Q000235:genetics* / Q000401:mortality; D010641:Phenotype; D012720:Severity of Illness Index
chemical_list: D006684:HLA-DR Antigens; D015803:HLA-DR3 Antigen; D059811:HLA-DRB1 Chains