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Rheumatology 2000; 39: 1332-1336
© 2000 British Society for Rheumatology

Association of markers for TGFß3, TGFß2 and TIMP1 with systemic sclerosis

E. Susol, A. L. Rands1, A. Herrick, N. McHugh1, J. H. Barrett, W. E. R. Ollier and J. Worthington

ARC Epidemiology Unit, University of Manchester, Manchester and
1 Royal National Hospital for Rheumatic Diseases, Bath, UK

Objectives. To investigate whether six microsatellite markers known to map closely to genes involved in fibrosis are associated with systemic sclerosis (SSc).

Methods. Markers mapping to TGFß1, TGFß2, TGFß3, PDGFB, TIMP1 and COL5A2 were genotyped and allele frequency distributions compared in 191 patients and 196 controls. As TIMP1 maps to the X chromosome, male and females were analysed separately. Markers associated with SSc were further investigated according to whether patients had limited (lcSSc) or diffuse (dcSSc) cutaneous fibrosis.

Results. Associations were found between SSc and markers for TGFß3 ({chi}2=17.3, df=8, P=0.02), TGFß2 ({chi}2=25.2, df=13, P=0.02) and TIMP1 (with male SSc, {chi}2=11.9, df=5, P=0.03), between lcSSc and the TGFß2 marker ({chi}2=25.6, df=13, P=0.02), and between dcSSc and TGFß3 marker ({chi}2=27.1, df=8, P=0.001). Between lcSSc and dcSSc patients, the allele frequency distribution differed only for the TGFß3 marker ({chi}2=16.5, df=6, P=0.01).

Conclusion. These associations indicate a possible role for TGFß3, TGFß2 and TIMP1 in genetic susceptibility to SSc and for TGFß3 in determining the degree of cutaneous fibrosis.

KEY WORDS: Systemic sclerosis, TGFß, TIMP, Fibrosis, Microsatellite markers.

Correspondence to: E. Susol, ARC Epidemiology Unit, University of Manchester, Stopford Building, Oxford Road, Manchester M13 9PT, UK.


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