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.
