title: Modifying effects of HLA-DRB1 allele interactions on age at onset of multiple sclerosis in Western Australia.
abstract: The contribution of genetic factors to the age at onset in multiple sclerosis is poorly understood. Our objective was to investigate the disease modifying effects of HLA-DRB1 alleles and allele interactions on age at onset of multiple sclerosis. High-resolution four-digit HLA-DRB1 genotyping was performed in a cohort of 461 multiple sclerosis patients from the Perth Demyelinating Diseases Database. Carriage of the HLA-DRB1*1501 risk allele was not significantly associated with age at onset but HLA-DRB1*0801 was associated with a later onset of the disease. The HLA-DRB1*0401 allele was associated with a reduced age at onset when combined with DRB1*1501 but may delay age at onset when combined with DRB1*0801. These findings indicate that epistatic interactions at the HLA-DRB1 locus have significant modifying effects on age at onset of multiple sclerosis and demonstrate the value of high-resolution genotyping in detecting such associations.
authors.affiliation: Centre of Neuromuscular and Neurological Disorders, University of Western Australia, Department of Neurology, Sir Charles Gairdner Hospital, Queen Elizabeth Medical Centre, Perth, Western Australia.
authors.forename: Jing-Shan
authors.initials: JS
authors.lastname: Wu
authors.forename: Wei
authors.initials: W
authors.lastname: Qiu
authors.forename: Alison
authors.initials: A
authors.lastname: Castley
authors.forename: Ian
authors.initials: I
authors.lastname: James
authors.forename: Frank L
authors.initials: FL
authors.lastname: Mastaglia
authors.forename: Frank T
authors.initials: FT
authors.lastname: Christiansen
authors.forename: William M
authors.initials: WM
authors.lastname: Carroll
authors.forename: Joyce
authors.initials: J
authors.lastname: Joseph
authors.forename: Allan G
authors.initials: AG
authors.lastname: Kermode
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D000368:Aged; D000483:Alleles; D002648:Child; D030541:Databases, Genetic; D005260:Female; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000453:epidemiology / Q000235:genetics*; D012044:Regression Analysis; D012737:Sex Factors; D014904:Western Australia / Q000453:epidemiology; D055815:Young Adult
chemical_list: D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553505:HLA-DRB1*04:01 antigen