title: Weight is an independent predictor of vascular injury in healthy volunteers with aspartate allele.
abstract: BACKGROUND
  Endothelial dysfunction and carotid intima-media thickeness (IMT) are currently considered key early events in atherogenesis and markers of arterial damage. We investigated whether endothelial nitric oxide synthase (eNOS) glutamate (Glu)298-aspartate (Asp) polymorphism may influence the vascular response to weight, as measured by BMI, in young, healthy individuals.
  
  
  METHODS
  One hundred young (30.6 ± 5.9 years) healthy individuals, without concomitant traditional cardiovascular risk factors took part in the study. Brachial artery endothelial function was assessed by vascular response to reactive hyperemia [flow-mediated dilation (FMD) and sublingual nitroglycerin (GTN)-mediated dilation] using high-resolution ultrasound. Carotid IMT was also measured.
  
  
  RESULTS
  Participants were grouped as Glu-homozygotes (n = 38) and Asp-carriers (n = 62). On univariate analysis, a higher response to GTN was associated with lower brachial baseline diameter (P < 0.001) and increasing value of high-density lipoprotein cholesterol (P = 0.04) in Asp-carriers, but not in Glu-homozygotes. Higher FMD correlated with lower brachial baseline diameter (P < 0.001), BMI (P = 0.03) and SBP (P = 0.03) in the Asp-carriers, but not in Glu-homozygotes. Higher IMT showed a similar Asp-genotype-dependent association with higher BMI (P = 0.001), SBP (P = 0.006) and DBP (P = 0.001). In individuals with Asp-alleles, the multivariate analysis showed that BMI was the only independent predictor of IMT.
  
  
  CONCLUSIONS
  Weight is independently associated with impaired arterial structure in healthy and genetically predisposed young individuals. The allelic variation (Asp298) of the eNOS gene polymorphism makes individuals vulnerable to the impact of weight on the development of atherosclerosis.
authors.affiliation: Consiglio Nazionale delle Ricerche, Institute of Clinical Physiology, Pasquinucci Hospital, Massa, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Paradossi
authors.forename: Olivia
authors.initials: O
authors.lastname: Manfrini
authors.forename: Enrica
authors.initials: E
authors.lastname: Ciofini
authors.forename: Carmine
authors.initials: C
authors.lastname: Pizzi
authors.forename: Andrea
authors.initials: A
authors.lastname: Biagini
authors.forename: Borejda
authors.initials: B
authors.lastname: Xhyheri
authors.forename: Maria G
authors.initials: MG
authors.lastname: Colombo
mesh_terms: D000328:Adult; D001224:Aspartic Acid; D050197:Atherosclerosis / Q000000981:diagnostic imaging / Q000201:enzymology / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D001835:Body Weight; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000503:physiopathology; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging / Q000201:enzymology / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D059168:Carotid Intima-Media Thickness; D016009:Chi-Square Distribution; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000503:physiopathology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D018698:Glutamic Acid; D006720:Homozygote; D006801:Humans; D007558:Italy; D016014:Linear Models; D008297:Male; D015999:Multivariate Analysis; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D009765:Obesity / Q000150:complications* / Q000503:physiopathology; D010641:Phenotype; D011110:Polymorphism, Genetic; D018570:Risk Assessment; D012307:Risk Factors; D014664:Vasodilation
chemical_list: D001224:Aspartic Acid; D018698:Glutamic Acid; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III