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

Abstract

Background. Polymorphisms within the gene for transforming growth factor (TGF)-β-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-β-1 polymorphic variants (C-509T, Leu10→Pro, Arg 25→Pro, Thr263→Ile) with albuminuria in uncomplicated essential hypertensive men, using (circulating active + acid-activatable latent) TGF-β-1 levels as an indirect index of their in vivo biological activity. Because of the close pathophysiological link of TGF-β-1 with the renin-angiotensin system, we also tested the behaviour of the angiotensin converting enzyme (ACE) deletioninsertion (DI) polymorphism.Methods. Albuminuria (three overnight collections), office and 24-h BP, left ventricular mass index (LVMI), BMI, renal function, glucose, lipids, plasma TGF-β-1 (n = 162, ELISA) were measured in 222 genetically unrelated, never-treated, uncomplicated Caucasian hypertensive men. ACE DI 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 μgmin) did not differ by TGF-β-1 genotypes, but both parameters were more frequent in ACE DD homozygotes. Plasma TGF-β-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 DI genotype, microalbuminuria was independent of TGF-β-1 polymorphism in this group of never-treated, uncomplicated essential hypertensive men.