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GENETIC SUSCEPTIBILITY TO MULTIPLE-SCLEROSIS LINKED TO MYELIN BASIC-PROTEIN GENE
Author(s): TIENARI PJ, WIKSTROM J, SAJANTILA A, PALO J, PELTONEN L
Source: LANCET    Volume: 340    Issue: 8826    Pages: 987-991    Published: OCT 24 1992  
Times Cited: 134     References: 29     
Abstract: 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.

Document Type: Article
Language: English
Reprint Address: TIENARI, PJ (reprint author), NATL PUBL HLTH INST, DEPT HUMAN MOLEC GENET, MANNERHEIMINTIE 166, SF-00300 HELSINKI, FINLAND
Addresses:
1. UNIV HELSINKI, DEPT NEUROL, SF-00100 HELSINKI 10, FINLAND
Publisher: LANCET LTD, 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL
Subject Category: Medicine, General & Internal
IDS Number: JV014
ISSN: 0140-6736
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