Genetic control of the circulating concentration of transforming growth factor type beta 1

The concentration of transforming growth factor beta (TGF- beta ) in plasma has been correlated with the development of several diseases, including atherosclerosis and certain forms of cancer. However, the mechanisms that control the concentration of TGF- beta in plasma are poorly understood. In a study of 170 pairs of female twins (average age 57.7 years) we show that the concentration of active plus acid-activatable latent TGF- beta 1 [(a+l) TGF- beta \m?\ is predominantly under genetic control (heritability estimate 0.54). Single strand conformation polymorphism (SSCP) mapping of the TGF- beta 1 gene promoter has identified two single base substitution polymorphisms. The two polymorphisms (G arrow right A at position -800 bp and C arrow right T at position -509 bp) are in linkage disequilibrium (correlation coefficient Delta = 0.215, P < 0.01). The C-509T polymorphism is significantly associated with the plasma concentration of (a+l) TGF- beta 1, explaining 8.2% of the additive genetic variance of (a+l) TGF- beta 1 concentration. It is therefore possible that predisposition to atherosclerosis, bone diseases or various forms of cancer may be correlated with the presence of particular alleles at the TGFB1 locus.