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NEUROLOGY 1998;51:748-753
© 1998 American Academy of Neurology

A systematic study of oligodendrocyte growth factors as candidates for genetic susceptibility to MS

C. Mertens, MS, D. Brassat, MD, J. Reboul, BS, S. Eichenbaum-Voline, MS, C. Vuillemin-Azais, MD, I. Cournu, BS, M. C. Babron, PhD, G. Semana, MD, G. Edan, MD, M. Clanet, MD, F. Clerget-Darpoux, PhD, A. Baron-Van Evercooren, PhD, O. Lyon-Caen, MD, R. Liblau, MD, PhD, B. Fontaine, MD, PhD and The French Multiple Sclerosis Genetics Group

From INSERM CJF9608 (Drs. Mertens, Brassat, Cournu, Baron-Van Evercooren, Liblau, and Fontaine), Laboratoire d'Immunologie Cellulaire (Drs. Reboul and Liblau), Fédération de Neurologie (Drs. Lyon-Caen and Fontaine), INSERM U360 (Dr. Lyon-Caen), Groupe Hospitalier Pitié-Salpêtrière, Paris; INSERM U155 (Drs. Eichenbaum-Voline, Babron, and Clerget-Darpoux), Château de Longchamp, Paris; Service de Neurologie (Drs. Brassat and Clanet), Hôpital Purpan, Toulouse; and Services de Neurologie et d'Immunologie (Drs. Semana and Edan), Hôpital Pontchaillou, Rennes, France.

Address correspondence and reprint requests to Dr: Bertrand Fontaine, INSERM CJF9608, Bâtiment de la Nouvelle Pharmacie, Hôpital de la Salpêtrière, 47 Bd Hôpital, 75013 Paris, France.

Objective: To test 23 genes coding for growth factors and their receptors as candidates for MS genetic susceptibility in 84 multiplex families of French origin by linkage analysis.

Background: Epidemiologic studies have indicated that genetic susceptibility in MS exists. To identify MS susceptibility genes, association and linkage studies were performed with candidate genes suggested by the pathology of MS. The most consistent result was genetic association and linkage of MS to human leukocyte antigen (HLA) DR15. Recent advances in the knowledge of MS pathology have suggested that the oligodendrocyte, the myelin-forming cell in the CNS, and its growth factors might play a crucial role in MS.

Methods: Fifty-two polymorphic markers within or flanking 23 candidate genes were used. Data were analyzed with the maximum likelihood score (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 0.93) were observed for transforming growth factor beta 3 (TGFß3) in HLA DR15-associated families, suggesting a possible role for this growth factor in interaction with HLA.

Conclusions: Oligodendrocyte growth factors do not play a significant role in MS genetic susceptibility, at least in the tested sample. TGFß3, the only gene highlighted by this study, deserves further analysis.

The authors thank ARSEP, AFM-Généthon, GREG and DRC AP-HP(contract 960004) for financial support and technical assistance. C. Mertens was supported by a fellowship from ARSEP and CAMPL.

Received February 19, 1998. Accepted in final form May 1, 1998.




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