title: eNOS and caveolin-1 gene polymorphisms interaction and intima media thickness: a proof of concept study in ESRD patients.
abstract: BACKGROUND
  Caveolae are a prominent microdomain in endothelial cells and appropriate localization in caveolae is fundamental for endothelial nitric oxide synthase (eNOS) activity. Since the Glu298Asp variant in the eNOS gene alters caveolar localization of the corresponding enzyme, we tested the interaction between this variant and the rs4730751 polymorphism of the caveolin-1 (CAV-1) gene as related to arterial remodeling in end-stage renal disease (ESRD) patients.
  
  
  METHODS
  One hundred and thirty-three ethnically homogeneous ESRD patients underwent carotid ultrasonographic studies to measure intima-media thickness (IMT) and carotid cross-sectional area (CSA). Genotyping was performed by high-throughput allelic discrimination assays on real-time PCR.
  
  
  RESULTS
  Arterial remodeling was associated to the number of G alleles of CAV-1 polymorphism, GG homozygotes displaying an IMT and a CSA that were, respectively, 16% and 21% higher than those in patients without the risk allele (P < 0.012). In multiple linear regression analyses including the CAV-1 and the eNOS polymorphisms and adjusting for classical risk factors and risk factors peculiar to ESRD both polymorphisms were independent correlates of IMT (CAV-1: β = 0.20, P = 0.01; eNOS β = 0.25, P = 0.001) and CSA (CAV-1: β = 0.20, P = 0.01: eNOS β = 0.13, P = 0.09). Furthermore, strong interactions emerged between the two polymorphisms for explaining the variability in IMT (P = 0.001) and in CSA (P = 0.038) in these patients.
  
  
  CONCLUSIONS
  Overall these findings form preliminary evidence that disturbed interaction between CAV-1 and eNOS may be of relevance for arterial disease in ESRD and perhaps in other human diseases.
authors: CNR-IBIM, National Research Council-Institute of Biomedicine, Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, Reggio Calabria, Italy.
authors: Alessandra
authors: A
authors: Testa
authors: Belinda
authors: B
authors: Spoto
authors: Maria Cristina
authors: MC
authors: Sanguedolce
authors: Rosa M
authors: RM
authors: Parlongo
authors: Anna
authors: A
authors: Pisano
authors: Giovanni
authors: G
authors: Tripepi
authors: Francesco A
authors: FA
authors: Benedetto
authors: Francesca
authors: F
authors: Mallamaci
authors: Carmine
authors: C
authors: Zoccali
mesh_terms: D000328:Adult; D000368:Aged; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging / Q000473:pathology; D059168:Carotid Intima-Media Thickness; D051242:Caveolin 1 / Q000235:genetics*; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D011110:Polymorphism, Genetic
chemical_list: C495540:CAV1 protein, human; D051242:Caveolin 1; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III