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Contributo in rivista
Tipo: Articolo in rivista
Titolo: Combination of renin-angiotensin system polymorphisms is associated with altered renal sodium handling and hypertension.
Anno di pubblicazione: 2004
Autori: Siani A; Russo P; Cappuccio FP; Iacone R; Venezia A; Russo O; Barba G; Iacoviello L; Strazzullo P.
Affiliazioni autori: Epidemiology & Population Genetics, Institute of Food Sciences, CNR, Avellino, Italy; Department of Community Health Sciences, St. George's Hospital Medical School, London, UK; Department of Clinical & Experimental Medicine, Unit of Clinical Genetics and Pharmacology, Hypertension & Mineral Metabolism, "Federico II" University of Naples, Naples, Italy; and "Angela Valenti" Laboratory of Genetic and Environmental Risk Factors for Thrombotic Disease, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy.
Abstract: Genes of the renin-angiotensin-aldosterone system (RAAS) are natural candidates for sodium homeostasis and blood pressure regulation. To investigate the effect of a combination of polymorphisms of RAAS genes on renal sodium handling and blood pressure, 918 participants to the Olivetti Heart Study were genotyped for the following polymorphisms: I/D of angiotensin converting enzyme (ACE), M235T of angiotensinogen (AGT), A1166C of angiotensin II type-1 receptor (AT1R), and C-344T of aldosterone synthase (CYP11B2). The segmental renal sodium handling was evaluated by the fractional excretions of exogenous lithium (FE-Li), uric acid (FE-UA), and sodium (FE-Na). Twenty-eight carriers of triple homozygosity for M (AGT), A (AT1R), and C (CYP11B2) in the presence of the D allele of ACE (DD/ID) showed lower FE-Li (20.0%+/-5.9% versus 25.0%+/-7.5%; P=0.004; mean+/-sD), FE-UA (6.3%+/-2.0% versus 8.2%+/-2.7%; P=0.001), and FE-Na (0.96%+/-0.41% versus 1.22%+/-0.61%; P=0.004) as compared with all other allelic combinations (n=890), independently from age and body mass, suggesting an enhanced rate of proximal tubular sodium reabsorption. The carriers of the MM, AA, CC, DD/ID combination showed a substantially higher probability of being hypertensive (OR: 3.4 [(99% CI: 1.1 to 10.1]), independently of age and body mass. This relatively rare combination of allelic variants of candidate genes of the RAAS is associated with a significant alteration in proximal renal sodium handling and with higher risk of hypertension, suggesting that a combination of polymorphic variants at different candidate loci may affect phenotypic expression even in the absence of detectable effects of each variant at any single locus.
Lingua abstract: inglese
Pagine da: 598
Pagine a: 602
American Heart Association,
Numero volume: 43
Referee: Sė: Internazionale
Indicizzato da: ISI Web of Science (WOS) 
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