A SYSTEMATIC STUDY OF OLIGODENDROCYTE GROWTH-FACTORS AS CANDIDATES FOR GENETIC SUSCEPTIBILITY TO MS

Objective: To test 23 genes coding for growth factors and their recept ors as candidates for MS genetic susceptibility in 84 multiplex famili es of French origin by linkage analysis. Background: Epidemiologic stu dies have indicated that genetic susceptibility in MS exists. To ident ify MS susceptibility genes, association and linkage studies were perf ormed with candidate genes suggested by the pathology of MS. The most consistent result was genetic association and linkage of MS to human l eukocyte antigen (HLA) DR15. Recent advances in the knowledge of MS pa thology have suggested that the oligodendrocyte, the myelin-forming ce ll in the CNS, and its growth factors might play a crucial role in MS. Methods: Fifty-two polymorphic markers within or flanking 23 candidat e genes were used. Data were analyzed with the maximum likelihood scor e (MLS) approach. We also searched for a genetic interaction with HLA. Results: Negative results were obtained for all candidate genes. The lower limits of the relative risk (lambda s) possibly excluded for any candidate gene ranged from 1.3 to 2.8. Positive MLS values (up to 0.9 3) were observed for transforming growth factor beta 3 (TGF beta 3) in HLA DR15-associated families, suggesting a possible role for this gro wth factor in interaction with HLA. Conclusions: Oligodendrocyte growt h factors do not play a significant role in MS genetic susceptibility, at least in the tested sample. TGF beta 3, the only gene highlighted by this study, deserves further analysis.