Modifying effects of HLA-DRB1 allele interactions on age at onset of multiple sclerosis in Western Australia.
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.
Wu
Jing-Shan
JS
Centre of Neuromuscular and Neurological Disorders, University of Western Australia, Department of Neurology, Sir Charles Gairdner Hospital, Queen Elizabeth Medical Centre, Perth, Western Australia.
Qiu
Wei
W
Castley
Alison
A
James
Ian
I
Mastaglia
Frank L
FL
Christiansen
Frank T
FT
Carroll
William M
WM
Joseph
Joyce
J
Kermode
Allan G
AG
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
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553505:HLA-DRB1*04:01 antigen