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).

Conclusion: 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.

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.