Association of markers for TGFβ3, TGFβ2 and TIMP1 with systemic sclerosis

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 TGFβ1, TGFβ2, TGFβ3, 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 TGFβ3 (χ2=17.3, df=8, P=0.02), TGFβ2 (χ2=25.2, df=13, P=0.02) and TIMP1 (with male SSc, χ2=11.9, df=5, P=0.03), between lcSSc and the TGFβ2 marker (χ2=25.6, df=13, P=0.02), and between dcSSc and TGFβ3 marker (χ2=27.1, df=8, P=0.001). Between lcSSc and dcSSc patients, the allele frequency distribution differed only for the TGFβ3 marker (χ2=16.5, df=6, P=0.01).

Conclusion. These associations indicate a possible role for TGFβ3, TGFβ2 and TIMP1 in genetic susceptibility to SSc and for TGFβ3 in determining the degree of cutaneous fibrosis.