In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 100, No. 25 ( 2003-12-09), p. 15041-15046
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 ( CD24 v ) in the mature protein. We found that the CD24 v/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 CD24 v/v patients with expanded disability status scale 6.0 reached the milestone in 5 years, whereas the CD24 a/v ( P = 0.00037) and CD24 a/a ( P = 0.0016) patients did so in 16 and 13 years, respectively. Moreover, our data suggest that the CD24 v/v patients expressed higher levels of CD24 on peripheral blood T cells than did the CD24 a/a patients. Transfection with CD24 a and CD24 v cDNA demonstrated that the CD24 v allele can be expressed at higher efficiency than the CD24 a 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.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.2533866100
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2003
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
