title: Lack of association between TGF-beta-1 genotypes and microalbuminuria in essential hypertensive men.
abstract: BACKGROUND
  Polymorphisms within the gene for transforming growth factor (TGF)-beta-1, a pro-fibrogenic cytokine pathophysiologically involved in hypertension and hypertensive target damage, might modulate the biological activity of the encoded protein. Through that mechanism, they might contribute to microalbuminuria, a marker of subclinical renal damage and a correlate of systemic inflammation and endothelial dysfunction in hypertension, a possibility never before tested. For this reason, we assessed the association of four TGF-beta-1 polymorphic variants (C-509T, Leu(10)-->Pro, Arg(25)-->Pro, Thr(263)-->Ile) with albuminuria in uncomplicated essential hypertensive men, using (circulating active + acid-activatable latent) TGF-beta-1 levels as an indirect index of their in vivo biological activity. Because of the close pathophysiological link of TGF-beta-1 with the renin-angiotensin system, we also tested the behaviour of the angiotensin converting enzyme (ACE) deletion/insertion (D/I) polymorphism.
  
  
  METHODS
  Albuminuria (three overnight collections), office and 24-h BP, left ventricular mass index (LVMI), BMI, renal function, glucose, lipids, plasma TGF-beta-1 (n = 162, ELISA) were measured in 222 genetically unrelated, never-treated, uncomplicated Caucasian hypertensive men. ACE D/I polymorphisms were analysed by the polymerase chain reaction technique or a 5' nuclease assay with further restriction analysis when required.
  
  
  RESULTS
  Urine albumin levels or microalbuminuria (albuminuria > or =15 microg/min) did not differ by TGF-beta-1 genotypes, but both parameters were more frequent in ACE D/D homozygotes. Plasma TGF-beta-1 was similar across genetic backgrounds and was unrelated to albuminuria. Cardiovascular, renal, metabolic parameters were homogeneously distributed across genotypes.
  
  
  CONCLUSIONS
  In contrast to its link with the ACE D/I genotype, microalbuminuria was independent of TGF-beta-1 polymorphism in this group of never-treated, uncomplicated essential hypertensive men.
authors.affiliation: Dipartimento Cardio Toracico e Vascolare, Università di Pisa, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Dell'Omo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Penno
authors.forename: Laura
authors.initials: L
authors.lastname: Pucci
authors.forename: Daniela
authors.initials: D
authors.lastname: Lucchesi
authors.forename: Stefano
authors.initials: S
authors.lastname: Del Prato
authors.forename: Roberto
authors.initials: R
authors.lastname: Pedrinelli
mesh_terms: D000328:Adult; D000419:Albuminuria / Q000097:blood / Q000209:etiology* / Q000235:genetics*; D000483:Alleles; D019943:Amino Acid Substitution; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000150:complications* / Q000235:genetics*; D054643:INDEL Mutation; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D053773:Transforming Growth Factor beta1 / Q000097:blood / Q000235:genetics*
chemical_list: D017931:DNA Primers; D053773:Transforming Growth Factor beta1; D007703:Peptidyl-Dipeptidase A