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 TGFbeta1, TGFbeta2, TGFbeta3, 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 TGFbeta3 (chi(2)=17.3, df=8, P=0.02), TGFbeta2 (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 TGFbeta3 marker (chi(2)=27.1, df=8, P=0.001). Between lcSSc and dcSSc patients, the allele frequency distribution differed only for the TGFbeta3 marker (chi(2)=16.5, df=6, P=0.01).
Conclusion: These associations indicate a possible role for TGFbeta3, TGFbeta2 and TIMP1 in genetic susceptibility to SSc and for TGFbeta3 in determining the degree of cutaneous fibrosis.