High-resolution HLA-DRB1 genotyping in an Australian inclusion body myositis (s-IBM) cohort: an analysis of disease-associated alleles and diplotypes.
We performed high-resolution (4-digit) HLA-DRB1 genotyping in an Australian cohort of 105s-IBM patients and 189 controls. Our findings showed that whilst the strongest association was with the HLA-DRB1*03:01 allele and the HLA-DRB1*03:01/*01:01 diplotype, HLA-DRB1*01:01 and HLA-DRB1*13:01 are also risk alleles. A number of other alleles, HLA-DRB1*04:01, *04:04, *07:01, *09:01, *11:01 and *15:01, as well as the HLA-DRB1*03:01/*04:01 and HLA-DRB1*03:01/*07:01 diplotypes were reduced in s-IBM cases and may be protective. The HLA-DRB1*03:01 and HLA-DRB1*13:01 alleles also appear to have an influence on the age at onset of the disease and severity of muscle weakness. Our findings indicate that the influence of HLA-DRB1 in s-IBM is complex and that epistatic interactions at the HLA-DRB1 locus contribute both to disease susceptibility and to the clinical phenotype.
Australian Neuro-muscular Research Institute and Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Queen Elizabeth II Medical Centre, Perth, Western Australia, Australia.
Arada
A
Rojana-udomsart
Ian
I
James
Alison
A
Castley
Merrilee
M
Needham
Adrian
A
Scott
Timothy
T
Day
Lynette
L
Kiers
Alastair
A
Corbett
Carolyn
C
Sue
Campbell
C
Witt
Patricia
P
Martinez
Frank
F
Christiansen
Frank
F
Mastaglia
D000483:Alleles; D001315:Australia; D015331:Cohort Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D018979:Myositis, Inclusion Body / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012307:Risk Factors
D059811:HLA-DRB1 Chains