title: Genetic control of the circulating concentration of transforming growth factor type beta1.
abstract: 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-beta1 [(a+l) TGF-beta therefore is predominantly under genetic control (heritability estimate 0.54). Single strand conformation polymorphism (SSCP) mapping of the TGF-beta1 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 Delta = 0.215, P < 0.01). The C-509T polymorphism is significantly associated with the plasma concentration of (a+l) TGF-beta1, explaining 8.2% of the additive genetic variance of (a+l) TGF-beta1 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.
authors.affiliation: Department of Medicine, University of Cambridge, Box 157, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK.
authors.forename: D J
authors.initials: DJ
authors.lastname: Grainger
authors.forename: K
authors.initials: K
authors.lastname: Heathcote
authors.forename: M
authors.initials: M
authors.lastname: Chiano
authors.forename: H
authors.initials: H
authors.lastname: Snieder
authors.forename: P R
authors.initials: PR
authors.lastname: Kemp
authors.forename: J C
authors.initials: JC
authors.lastname: Metcalfe
authors.forename: N D
authors.initials: ND
authors.lastname: Carter
authors.forename: T D
authors.initials: TD
authors.lastname: Spector
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001161:Arteriosclerosis / Q000097:blood / Q000235:genetics; D001483:Base Sequence; D001847:Bone Diseases / Q000097:blood / Q000235:genetics; D004247:DNA / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D006801:Humans; D015810:Linkage Disequilibrium; D008875:Middle Aged; D008957:Models, Genetic; D009369:Neoplasms / Q000097:blood / Q000235:genetics; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic; D016212:Transforming Growth Factor beta / Q000097:blood* / Q000235:genetics*; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic
chemical_list: D017931:DNA Primers; D016212:Transforming Growth Factor beta; D004247:DNA