Genetic control of the circulating concentration of transforming growth factor type beta1

The concentration of transforming growth factor beta (TGF-beta) in plasmahas been correlated with the development of several diseases, includingatherosclerosis and certain forms of cancer. However, the mechanisms thatcontrol the concentration of TGF-beta in plasma are poorly understood. In astudy of 170 pairs of female twins (average age 57.7 years) we show thatthe concentration of active plus acid- activatable latent TGF-beta1 [(a+l)TGF-beta therefore is predominantly under genetic control (heritabilityestimate 0.54). Single strand conformation polymorphism (SSCP) mapping ofthe TGF-beta1 gene promoter has identified two single base substitutionpolymorphisms. The two polymorphisms (G-->A at position -800 bp andC-->T at position -509 bp) are in linkage disequilibrium (correlationcoefficient Delta = 0.215, P < 0.01). The C-509T polymorphism issignificantly associated with the plasma concentration of (a+l) TGF-beta1,explaining 8.2% of the additive genetic variance of (a+l) TGF-beta1concentration. It is therefore possible that predisposition toatherosclerosis, bone diseases or various forms of cancer may be correlatedwith the presence of particular alleles at the TGFB1 locus.