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 (I, 2 and 3) , is a strongly immunosuppressive cytokine-inhibiting expression of pro-inf lammatory cytokines and blocking cytokine induction of adhesion molecules. TGF-beta delays onset of EAE and TGF-beta 1 gene knockout mice develop fata l multifocal inflammatory disease. High TGF-beta levels exist during MS rem ission whilst E-selectin, whose expression is inhibited by TGF-beta is foun d at higher levels in primary Progressive disease (PPMS) and it is postulat ed that the unremitting course of PPMS may be due to low levels of TGF-beta . Methods: Gene association studies using separate polymorphic microsatelli te markers for TGF-beta 1 and TGF-beta 2 were performed incorporating 151 r elapsing-remitting or secondary progressive MS (RR/SPMS) patients 104 PPMS patients and 159 normal controls (Nor). Forward primers were 5' end-labelle d with 6-Fam, PCR products were analysed on on Applied Biosystems 373A fluo rescent fragment analyser and Genescan 672 software was used for allele siz ing. Results: No significant differences existed in allele frequencies betw een either MS group and controls regarding the TGF-beta 1 marker: RR/SPMS v s Nor (P=0.48, df=8); PPMS vs Nor (P=0.34, df=8). Similarly there were no a ssociations demonstrated with the TGF-PZ marker: RR/SPMS vs Nor (P=0.24, df =2); PPMS vs Nor (P=0.53, df=2). Conclusion: These data indicate that TGF-b eta 1 and beta 2 genes are not loci influencing MS susceptibility, either R R/SPMS or PPMS in this population.