CD24 Polymorphism and multiple sclerosis

University Of Michigan At Ann Arbor, Ann Arbor MI

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Abstract

[unreadable] DESCRIPTION (provided by applicant): Multiple sclerosis (MS) is a chronic autoimmune disease with an incidence of 1/1000 in white Caucasians. The risk of MS, however, increases by >30 fold among first-degree relatives of an affected individual and approximately 300-fold among individuals with an affected monozygotic twin. While linkage studies have implicated multiple loci throughout the human genome that may affect the susceptibility to MS, the HIA-DR locus remains the only known one with consistent linkage to MS. Moreover, the previous mapping studies have not taken into full account the heterogeneity of MS and may have therefore left out genetic modifiers that control the severity of MS. Since MS genes are likely to have low penetrances and are affected by a large number of genetic modifiers, insight from mouse genetic studies may be valuable to identify the genes and/or their modifiers. We have recently demonstrated that mouse CD24 controls a critical checkpoint for the development of experimental autoimmune encephalomyelitis (EAE), a mouse model for human multiple sclerosis. Moreover, the human CD24 gene has a functional polymorphism due to a non-conserved amino acid substitution in a critical position of the CD24 protein. To test whether polymorphism of CD24 is a risk factor for the incidence and clinical course of multiple sclerosis, we have carried out preliminary studies using more than 700 blood samples from multiple sclerosis patients and normal controls. Our results demonstrated that the homozygocity of CD24v/v resulted in an increase of about 2 in the relative risk of MS. The association between MS and CD24 genotype is also substantiated by our transmission-disequilibrium test (TDT). The main goal of this study is to establish the contribution of CD24 polymorphism to the incidence and clinical course of MS and to determine the molecular basis by which the polymorphism of the CD24 gene contributed to the pathogenesis of MS. Our results will have important implications for the diagnosis and treatment of MS. [unreadable] [unreadable]