Association of markers for TGF beta 3, TGF beta 2 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 sclerosi s (SSc). Methods. Markers mapping to TGF beta1, TGF beta2, TGF beta3, PDGFB, TIMP1 a nd COL5A2 were genotyped and allele frequency distributions compared in 191 patients and 196 controls. As TIMP1 maps to the X chromosome, male and fem ales were analysed separately, Markers associated with SSc were further inv estigated according to whether patients had limited (lcSSc) or diffuse (dcS Sc) cutaneous fibrosis. Results. Associations were found between SSc and markers for TGF beta3 (chi (2) = 17.3, df = 8, P = 0.02), TGF beta2 (chi (2) = 25.2, df = 13, P = 0.0 2) and TIMP1 (with male SSc, chi (2) = 11.9, df = 5, P = 0.03), between lcS Sc and the TGF beta2 marker (chi (2) = 25.6, df = 13, P = 0.02), and betwee n dcSSc and TGF beta3 marker (chi (2) = 27.1, df = 8, P = 0.001). Between l cSSc and dcSSc patients, the allele frequency distribution differed only fo r the TGF beta3 marker (chi (2) = 16.5, df = 6, P = 0.01). Conclusion. These associations indicate a possible role for TGF beta3, TGF beta2 and TIMP1 in genetic susceptibility to SSc and for TGF beta3 in deter mining the degree of cutaneous fibrosis.