title: Genome wide differences of gene expression associated with HLA-DRB1 genotype in multiple sclerosis: a pilot study.
abstract: Using two microarray platforms, we identify HLA-DRB5 as the most highly expressed gene in MS compared to healthy subjects. As expected, HLA-DRB5 expression was associated with the HLA-DRB1*1501 MS susceptibility allele. Besides HLA-DRB5, there were 1219 differentially expressed exons (p<0.01, |fold change (FC)|>1.2) that differed between HLA-DRB1*1501 Positive multiple sclerosis subjects (MSP) compared to HLA-DRB1*1501 negative multiple sclerosis subjects (MSN). Analysis of the regulated genes revealed significantly different immune signaling pathways including IL-4 and IL-17 in these two MS genotypes. Different risk alleles appear to be associated with different patterns of gene expression that may reflect differences in pathophysiology of these two MS subtypes. These preliminary data will need to be confirmed in future studies.
authors.affiliation: Department of Neurology and the M.I.N.D. Institute, University of California at Davis, Sacramento, CA 95817, USA. michelle.apperson@ucdmc.ucdavis.edu
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Apperson
authors.forename: Yingfang
authors.initials: Y
authors.lastname: Tian
authors.forename: Boryana
authors.initials: B
authors.lastname: Stamova
authors.forename: Bradley P
authors.initials: BP
authors.lastname: Ander
authors.forename: Glen C
authors.initials: GC
authors.lastname: Jickling
authors.forename: Mark A
authors.initials: MA
authors.lastname: Agius
authors.forename: Frank R
authors.initials: FR
authors.lastname: Sharp
mesh_terms: D000328:Adult; D000483:Alleles; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D059811:HLA-DRB1 Chains / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D010865:Pilot Projects; D055815:Young Adult
chemical_list: D059811:HLA-DRB1 Chains; C489631:HLA-DRB1*15:01 antigen