TY - JOUR
T1 - CD24 is a genetic modifier for risk and progression of multiple sclerosis
AU - Zhou, Qunmin
AU - Rammohan, Kottil
AU - Lin, Shili
AU - Robinson, Nikki
AU - Li, Ou
AU - Liu, Xingluo
AU - Bai, Xue Feng
AU - Yin, Lijie
AU - Scarberry, Bruce
AU - Du, Peishuang
AU - You, Ming
AU - Guan, Kunliang
AU - Zheng, Pan
AU - Liu, Yang
PY - 2003/12/9
Y1 - 2003/12/9
N2 - 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.
AB - 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.
KW - Autoimmunity
KW - Costimulatory molecules
KW - Disease susceptibility
KW - Single-nucleotide polymorphism
KW - T lymphocytes
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U2 - 10.1073/pnas.2533866100
DO - 10.1073/pnas.2533866100
M3 - Article
C2 - 14657362
AN - SCOPUS:10744223574
SN - 0027-8424
VL - 100
SP - 15041
EP - 15046
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 25
ER -