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

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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, Arg25→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) 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-β-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 μg/min) did not differ by TGF-β-1 genotypes, but both parameters were more frequent in ACE D/D 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 D/I genotype, microalbuminuria was independent of TGF-β-1 polymorphism in this group of never-treated, uncomplicated essential hypertensive men.

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