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

The concentration of transforming growth factor beta (TGF-beta) in plasma h as been correlated with the development of several diseases, including athe rosclerosis and certain forms of cancer. However, the mechanisms that contr ol the concentration of TGF-beta in plasma are poorly understood. In a stud y of 170 pairs of female twins (average age 57.7 years) we show that the co ncentration of active plus acid-activatable latent TGF-beta 1 [(a+l) TGF-be ta therefore is predominantly under genetic control (heritability estimate 0.54). Single strand conformation polymorphism (SSCP) mapping of the TGF-be ta 1 gene promoter has identified two single base substitution polymorphism s. The two polymorphisms (G-->A at position -800 bp and C-->T at position - 509 bp) are in linkage disequilibrium (correlation coefficient Delta = 0.21 5, 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 g enetic 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 TGF B1 locus.