I polimorfismi del gene dell’enzima di conversione dell’angiotensina (ACE) nel rene policistico autosomico dominante (ADPKD)

BACKGROUND. In the kidneys of patients with progressive IgA Nephropathy (IgAN) hyperactivation of angiotensin II has been recognized. We analyzed the role of the Renin Angiotensin System (RAS) polymorphisms in relation to renal histology in a Northern Italian population. Furthermore we evaluated the effect of the genetic variants on tissutal expression levels of the respective genes.METHODS. The clinical data at the biopsy time and the histological data of 121 patients affected by IgA nephropathy were collected, 97 of these subjects and 100 healthy control subjects were genotyped for the following polymorphisms: Angiotensinogen (Agt) M235T, Angiotensin Converting Enzyme (ACE) I/D, Angiotensin II type 1 Receptor (AT1R) A1166C variants. Twenty IgAN subjects were randomly selected for the mRNA expression evaluation of the genes Agt, ACE and AT1R.RESULTS. None of the polymorphisms seems associated with the risk of developing IgAN when compared to the control population. The Agt M235T is associated to the mesangial proliferation, (Kruskal-Wallis KW = 7.907 corrected for ties, p value 0.019), the TT variant presents the highest value of mesangioproliferative lesions. The ACE genotype is related to glomerulosclerosis and glomerular volume: patients with the II genotype show a major grade of glomerulosclerosis (Kruskal Wallis χ2 9.225, df 2, p 0.01) and largest glomeruli (p = 0.003). Glomerular ACE mRNA levels are significantly higher in patients with the ACE-II genotype than in carriers of the DD and DI genotypes (p=0.04). CONCLUSION. This study suggests that RAS genetic variants may modulate proliferative and sclerotic phenomena by affecting the tissutal abundance of the RAS components.