A systematic study of oligodendrocyte growth factors as candidates for genetic susceptibility to MS. French Multiple Sclerosis Genetics Group.
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 (Xs) 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 (TGFbeta3) 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. TGFbeta3, the only gene highlighted by this study, deserves further analysis.
Mertens
C
C
INSERM CJF9608, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Brassat
D
D
Reboul
J
J
Eichenbaum-Voline
S
S
Vuillemin-Azais
C
C
Cournu
I
I
Babron
M C
MC
Semana
G
G
Edan
G
G
Clanet
M
M
Clerget-Darpoux
F
F
Baron-Van Evercooren
A
A
Lyon-Caen
O
O
Liblau
R
R
Fontaine
B
B
D000328:Adult; D004198:Disease Susceptibility; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D006133:Growth Substances / Q000235:genetics*; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000235:genetics*; D009836:Oligodendroglia / Q000378:metabolism*; D011110:Polymorphism, Genetic; D017978:Receptors, Growth Factor / Q000235:genetics*; D012306:Risk
D006133:Growth Substances; D017978:Receptors, Growth Factor