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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&lt; 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 theTGFB1locus.

Genetic Control of the Circulating Concentration of Transforming Growth Factor Type β1