Lack of association between TGF-beta-1 genotypes and microalbuminuria in essential hypertensive men

作者：Dell'Omo Giulia; Penno Giuseppe; Pucci Laura; Lucchesi Daniela; Del Prato Stefano; Pedrinelli Roberto^*

来源：Nephrology Dialysis Transplantation, 2009, 24(6): 1864-1869.

DOI：10.1093/ndt/gfn754

• angiotensin converting enzyme deletion
• insertion polymorphism
• circulating TGF-beta-1 levels
• hypertensive target organ damage
• microalbuminuria
• TGF-beta-1 polymorphisms

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 >= 15 mu g/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.

• 出版日期2009-6