Lack of association of transforming growth factor (TGF)-b1 and b2 gene polymorphisms with multiple sclerosis (MS) in Northern Ireland

Abstract

Objective: To examine the influence of TGF-b genes on MS susceptibility. Background: TGF-b, 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-b delays onset of EAE and TGF-b1 gene knockout mice develop fatal multifocal inflammatory disease. High TGF-b levels exist during MS remission whilst E-selectin, whose expression is inhibited by TGF-b, 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-b. Methods: Gene association studies using separate polymorphic microsatellite markers for TGF-b1 and TGF-b2 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-b1 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-b2 marker: RR/SPMS vs Nor (P=0.24, df=2); PPMS vs Nor (P=0.53, df=2). Conclusion: These data indicate that TGF-b1 and b2 genes are not loci influencing MS susceptibility, either RR/SPMS or PPMS, in this population.

Keywords

multiple sclerosis primary progressive multiple sclerosis transforming growth factor-b association studies genes cytokines

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