title: CD24 is a genetic modifier for risk and progression of multiple sclerosis.
abstract: Multiple sclerosis (MS) is a chronic neurological disease of unknown etiology, but a genetic basis for the disease is undisputed. We have reported that CD24 is required for the pathogenicity of autoreactive T cells in experimental autoimmune encephalomyelitis, the mouse model of MS. Here we investigate the contribution of CD24 to MS by studying single-nucleotide polymorphism in the ORF among 242 MS patients and 207 population controls. This single-nucleotide polymorphism results in replacement of alanine (CD24a) with valine (CD24v) in the mature protein. We found that the CD24v/v renders a >2-fold increase in the relative risk of MS in the general population (P = 0.023). Among familial MS, the CD24v allele is preferentially transmitted into affected individuals (P = 0.017). Furthermore, 50% of CD24v/v patients with expanded disability status scale 6.0 reached the milestone in 5 years, whereas the CD24a/v (P = 0.00037) and CD24a/a (P = 0.0016) patients did so in 16 and 13 years, respectively. Moreover, our data suggest that the CD24v/v patients expressed higher levels of CD24 on peripheral blood T cells than did the CD24a/a patients. Transfection with CD24a and CD24v cDNA demonstrated that the CD24v allele can be expressed at higher efficiency than the CD24a alleles. Thus, CD24 polymorphism is a genetic modifier for susceptibility and progression of MS in the central Ohio cohort that we studied, perhaps by affecting the efficiency of CD24 expression on the cell surface.
authors.affiliation: Division of Cancer Immunology and Department of Pathology, Ohio State University, Columbus, OH 43210, USA.
authors.forename: Qunmin
authors.initials: Q
authors.lastname: Zhou
authors.forename: Kottil
authors.initials: K
authors.lastname: Rammohan
authors.forename: Shili
authors.initials: S
authors.lastname: Lin
authors.forename: Nikki
authors.initials: N
authors.lastname: Robinson
authors.forename: Ou
authors.initials: O
authors.lastname: Li
authors.forename: Xingluo
authors.initials: X
authors.lastname: Liu
authors.forename: Xue-feng
authors.initials: XF
authors.lastname: Bai
authors.forename: Lijie
authors.initials: L
authors.lastname: Yin
authors.forename: Bruce
authors.initials: B
authors.lastname: Scarberry
authors.forename: Peishuang
authors.initials: P
authors.lastname: Du
authors.forename: Ming
authors.initials: M
authors.lastname: You
authors.forename: Kunliang
authors.initials: K
authors.lastname: Guan
authors.forename: Pan
authors.initials: P
authors.lastname: Zheng
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000409:Alanine / Q000737:chemistry; D000483:Alleles; D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000502:physiology*; D051927:CD24 Antigen; D017252:CD3 Complex / Q000096:biosynthesis; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics; D005434:Flow Cytometry; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008562:Membrane Glycoproteins; D051379:Mice; D008957:Models, Genetic; D009103:Multiple Sclerosis / Q000175:diagnosis* / Q000235:genetics*; D016366:Open Reading Frames; D010375:Pedigree; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013997:Time Factors; D014162:Transfection; D014633:Valine / Q000737:chemistry
chemical_list: D015703:Antigens, CD; D051927:CD24 Antigen; C497889:CD24 protein, human; D017252:CD3 Complex; C497890:Cd24a protein, mouse; D018076:DNA, Complementary; D008562:Membrane Glycoproteins; D014633:Valine; D000409:Alanine