GENETIC SUSCEPTIBILITY TO MULTIPLE-SCLEROSIS LINKED TO MYELIN BASIC-PROTEIN GENE

Genetic factors have been implicated in the aetiology of multiple sclerosis (MS), but the genes conferring susceptibility to MS have not been identified. We carried out genetic linkage and association analyses by studying polymorphism of the myelin basic protein (MBP) gene on chromosome 18, a candidate gene for MS, in 21 MS families, 51 additional unrelated patients with definite MS, and 85 controls. All subjects were Finnish, and 14 of the families were from an area with an exceptional familial clustering of MS. Magnetic resonance imaging (MRI) was used to examine subclinical disease in symptom-free family members. In the association analysis, the allele frequencies between MS patients and controls differed significantly, p = 0.000049), the difference being attributable mainly to a higher frequency of a 1.27 kb allele among patients. In the linkage analysis, based on an autosomal dominant model and penetrance 0.05, a maximum LOD score of 3.42 (theta = 0.00) was obtained when patients with optic neuritis and their symptom-free siblings with abnormal MRI findings were classified as "affected". When these subjects were classified as "unknown" the maximum LOD scores ranged from 2.99 to 3.25 (theta = 0.00). The results suggest that in this population genetic predisposition to MS is closely linked to the MBP gene and that polymorphism at the MBP locus or an adjacent locus has a role in the aetiology of MS.