This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by McDonnell, G V Articles by Graham, C A Search for Related Content PubMed PubMed Citation Articles by McDonnell, G V Articles by Graham, C A Social Bookmarking                         What's this?

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

Northern Ireland Regional Neurology Service, Royal Victoria Hospital, Belfast, Northern Ireland, UK

C W Kirk

Department of Medical Genetics, Belfast City Hospital Trust, Lisburn Road, Belfast, BT9 7AD, Northern Ireland, UK

S A Hawkins

Northern Ireland Regional Neurology Service, Royal Victoria Hospital, Belfast, Northern Ireland, UK, School of Clinical Medicine, The Queen's University of Belfast, Belfast, Northern Ireland, UK

C A Graham

Department of Medical Genetics, Belfast City Hospital Trust, Lisburn Road, Belfast, BT9 7AD, Northern Ireland, UK

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.

Key Words: multiple sclerosis • primary progressive multiple sclerosis • transforming growth factor-b • association studies • genes • cytokines

Multiple Sclerosis, Vol. 5, No. 2, 105-109 (1999)
DOI: 10.1177/135245859900500207


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?