title: A polymorphism at IGF1 locus is associated with carotid intima media thickness and endothelium-dependent vasodilatation.
abstract: OBJECTIVE
  Whether IGF-1 has a protective or a detrimental role in vascular homeostasis remains unsettled. There is evidence that the C/T polymorphism rs35767 near the promoter region of the IGF1 gene located in chromosome 12 is associated with plasma IGF-1 levels. We investigated the effects of this polymorphism on circulating IGF-1 levels, carotid intima media thickness (cIMT) and endothelial-dependent vasodilation.
  
  
  METHODS
  Two samples of adult nondiabetic Whites were studied. Sample 1 comprised 1124 individuals in whom cIMT was measured by ultrasonography. Sample 2 included 162 drug-naïve hypertensive individuals in whom endothelium-dependent and endothelium-independent vasodilation were assessed by intra-arterial infusion of acetylcholine (ACh), and sodium nitroprusside (SNP), respectively. IGF-1 was determined by chemiluminescent immunoassay. rs35767 polymorphism was screened using a TaqMan allelic discrimination assay.
  
  
  RESULTS
  In sample 1, IGF-1 levels were higher in subjects carrying the T allele compared with CC carriers (178 ± 78 vs. 166 ± 60 ng/mL, respectively; P = 0.007 adjusted for age, gender, and BMI). cIMT was lower in subjects carrying the T allele compared with CC carriers (0.71 ± 0.20 vs. 0.76 ± 0.22 mm, respectively; P < 0.0001 adjusted for age, gender, and BMI). In sample 2, maximally ACh-stimulated forearm blood flow was higher in subjects carrying the T allele compared with CC carriers (343 ± 191 vs. 281 ± 125%, respectively; P = 0.02 adjusted for age, gender, and BMI).
  
  
  CONCLUSIONS
  Subjects carrying the T allele exhibited significantly higher levels of circulating IGF-1, lower values of cIMT, and higher endothelium-dependent vasodilatation compared with CC carriers. These findings support the idea that IGF-1 plays a role in the pathogenesis of atherosclerosis.
authors.affiliation: Department of Medical and Surgical Sciences, University "Magna Graecia" of Catanzaro, Viale Europa, Catanzaro 88100, Italy. Electronic address: sesti@unicz.it.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Sesti
authors.affiliation: Department of Medical and Surgical Sciences, University "Magna Graecia" of Catanzaro, Viale Europa, Catanzaro 88100, Italy.
authors.forename: Gaia Chiara
authors.initials: GC
authors.lastname: Mannino
authors.affiliation: Department of Medical and Surgical Sciences, University "Magna Graecia" of Catanzaro, Viale Europa, Catanzaro 88100, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Andreozzi
authors.affiliation: Department of Medical and Surgical Sciences, University "Magna Graecia" of Catanzaro, Viale Europa, Catanzaro 88100, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Greco
authors.affiliation: Department of Medical and Surgical Sciences, University "Magna Graecia" of Catanzaro, Viale Europa, Catanzaro 88100, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Perticone
authors.affiliation: Department of Medical and Surgical Sciences, University "Magna Graecia" of Catanzaro, Viale Europa, Catanzaro 88100, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Sciacqua
authors.affiliation: Department of Systems Medicine, University of Rome-Tor Vergata, Italy.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Marini
authors.affiliation: Department of Medical and Surgical Sciences, University "Magna Graecia" of Catanzaro, Viale Europa, Catanzaro 88100, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Perticone
mesh_terms: D000109:Acetylcholine / Q000737:chemistry; D000328:Adult; D000483:Alleles; D050197:Atherosclerosis / Q000235:genetics*; D059168:Carotid Intima-Media Thickness; D015331:Cohort Studies; D004730:Endothelium, Vascular / Q000473:pathology*; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D049449:Luminescence; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside / Q000737:chemistry; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D014664:Vasodilation / Q000235:genetics*
chemical_list: D009599:Nitroprusside; D007334:Insulin-Like Growth Factor I; D000109:Acetylcholine
keywords: Atherosclerosis; Carotid intima media thickness; EDV; Endothelial dysfunction; FBF; IGF-1; SNP; cIMT; carotid intima media thickness; endothelial-dependent vasodilation; forearm blood flow; single nucleotide polymorphism