Sporadic inclusion body myositis: HLA-DRB1 allele interactions influence disease risk and clinical phenotype.
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.
Mastaglia
Frank L
FL
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
Needham
Merrilee
M
Scott
Adrian
A
James
Ian
I
Zilko
Paul
P
Day
Timothy
T
Kiers
Lynette
L
Corbett
Alastair
A
Witt
Campbell S
CS
Allcock
Richard
R
Laing
Nigel
N
Garlepp
Michael
M
Christiansen
Frank T
FT
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
D006684:HLA-DR Antigens; D015803:HLA-DR3 Antigen; D059811:HLA-DRB1 Chains