Lack of association of transforming growth factor (TGF)-beta 1 and beta 2 gene polymorphisms with multiple sclerosis (MS) in Northern Ireland.
OBJECTIVE
To examine the influence of TGF-beta genes on MS susceptibility.


BACKGROUND
TGF-beta, of which three homologous isoforms exist (1, 2 and 3), is a strongly immunosuppressive cytokine-inhibiting expression of pro-inflammatory cytokines and blocking cytokine induction of adhesion molecules. TGF-beta delays onset of EAE and TGF-beta 1 gene knockout mice develop fatal multifocal inflammatory disease. High TGF-beta levels exist during MS remission whilst E-selectin, whose expression is inhibited by TGF-beta, is found at higher levels in primary progressive disease (PPMS) and it is postulated that the unremitting course of PPMS may be due to low levels of TGF-beta.


METHODS
Gene association studies using separate polymorphic microsatellite markers for TGF-beta 1 and TGF-beta 2 were performed, incorporating 151 relapsing-remitting or secondary progressive MS (RR/SPMS) patients, 104 PPMS patients and 159 normal controls (Nor). Forward primers were 5' end-labelled with 6-Fam, PCR products were analysed on an Applied Biosystems 373A fluorescent fragment analyser and Genescan 672 software was used for allele sizing.


RESULTS
No significant differences existed in allele frequencies between either MS group and controls regarding the TGF-beta 1 marker: RR/SPMS vs Nor (P = 0.48, df = 8); PPMS vs Nor (P = 0.34, df = 8). Similarly there were no associations demonstrated with the TGF-beta 2 marker: RR/SPMS vs Nor (P = 0.24, df = 2); PPMS vs Nor (P = 0.53, df = 2).


CONCLUSIONS
These data indicate that TGF-beta 1 and beta 2 genes are not loci influencing MS susceptibility, either RR/SPMS or PPMS, in this population.
McDonnell
G V
GV
Northern Ireland Regional Neurology Service, Royal Victoria Hospital, Belfast, UK.
Kirk
C W
CW
Hawkins
S A
SA
Graham
C A
CA
D000483:Alleles; D004276:DNA, Satellite / Q000032:analysis; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D006579:Heterozygote; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000235:genetics*; D009660:Northern Ireland; D011110:Polymorphism, Genetic; D016212:Transforming Growth Factor beta / Q000235:genetics*
D004276:DNA, Satellite; D005819:Genetic Markers; D016212:Transforming Growth Factor beta