CD24 is a genetic modifier for risk and progression of multiple sclerosis

Qunmin Zhou, Kottil Rammohan, Shili Lin, Nikki Robinson, Ou Li, Xingluo Liu, Xue Feng Bai, Lijie Yin, Bruce Scarberry, Peishuang Du, Ming You, Kunliang Guan, Pan Zheng, Yang Liu

Research output: Contribution to journalArticle

93 Scopus citations

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 (CD24 a) 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 CD24 v 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 CD24 a 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.

Original languageEnglish (US)
Pages (from-to)15041-15046
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number25
DOIs
StatePublished - Dec 9 2003
Externally publishedYes

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Keywords

  • Autoimmunity
  • Costimulatory molecules
  • Disease susceptibility
  • Single-nucleotide polymorphism
  • T lymphocytes

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Zhou, Q., Rammohan, K., Lin, S., Robinson, N., Li, O., Liu, X., Bai, X. F., Yin, L., Scarberry, B., Du, P., You, M., Guan, K., Zheng, P., & Liu, Y. (2003). CD24 is a genetic modifier for risk and progression of multiple sclerosis. Proceedings of the National Academy of Sciences of the United States of America, 100(25), 15041-15046. https://doi.org/10.1073/pnas.2533866100