Document Detail

Combination of renin-angiotensin system polymorphisms is associated with altered renal sodium handling and hypertension.
MedLine Citation:
PMID:  14967847     Owner:  NLM     Status:  MEDLINE    
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.
Alfonso Siani; Paola Russo; Francesco Paolo Cappuccio; Roberto Iacone; Antonella Venezia; Ornella Russo; Gianvincenzo Barba; Licia Iacoviello; Pasquale Strazzullo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2004-02-16
Journal Detail:
Title:  Hypertension     Volume:  43     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2004 Mar 
Date Detail:
Created Date:  2004-02-27     Completed Date:  2004-05-24     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  598-602     Citation Subset:  IM    
Institute of Food Sciences, CNR, Via Roma, 52 A/C, 83100 Avellino, Italy.
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MeSH Terms
Gene Frequency
Genetic Predisposition to Disease
Hypertension / genetics*,  metabolism,  urine
Kidney Tubules, Proximal / metabolism*
Lithium / urine
Middle Aged
Polymorphism, Genetic*
Renin-Angiotensin System / genetics*
Sodium / metabolism,  urine*
Uric Acid / urine
Reg. No./Substance:
69-93-2/Uric Acid; 7439-93-2/Lithium; 7440-23-5/Sodium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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