Genetic control of the circulating concentration of transforming growth factor type β1

Abstract

The concentration of transforming growth factor β (TGF-β) 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-β 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-β1 [(a + l) TGF-β@? is predominantly under genetic control (heritability estimate 0.54). Single strand conformation polymorphism (SSCP) mapping of the TGF-β1 gene promoter has identified two single base substitution polymorphisms. The two polymorphisms (G→A at position -800 bp and C→T at position -509 bp) are in linkage disequilibrium (correlation coefficient Δ = 0.215, P < 0.01). The C-509T polymorphism is significantly associated with the plasma concentration of (a + l) TGF-β1, explaining 8.2% of the additive genetic variance of (a + l) TGF-β1 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.