Putative association of GPC5 polymorphism with the risk of inflammatory demyelinating diseases

Inflammatory demyelinating diseases (IDDs) are severe inflammatory diseases of the central nervous system (CNS) that cause loss of myelin in the nerve sheaths and axonal degeneration. IDDs include multiple sclerosis (MS) and neuromyelitis optica (NMO). MS affects the axons of the brain and spinal cord, while NMO primarily affects the optic nerves and spinal cord. Glypican 5 (GPC5) is known to be one of the susceptible genes for the risk of IDD, especially MS, based on genome-wide association studies (GWASs) and replication studies in Caucasians and African Americans. In the present study, in order to investigate the replicable genetic effects of GPC5 polymorphisms on the risk of IDD in Korean subjects, nine genetic variants were selected and genotyped in 237 normal controls and 178 IDD patients (including 79 MS and 99 NMO). Statistical analysis revealed that rs9523762 was associated with IDD and the association was retained even after correction for multiple testing (OR=1.68, P(corr)=0.03). Marginal association was also observed in rs1411751 (OR=0.54, P=0.02). In a subgroup analysis, rs1411751 was found to be associated with NMO (OR=0.36, P(corr)=0.03), and rs9523762 was marginally associated with both NMO and MS. These results indicate that GPC5 polymorphisms would be useful genetic indicators for IDDs, including NMO and MS.