A fasting insulin-raising allele at IGF1 locus is associated with circulating levels of IGF-1 and insulin sensitivity

Gaia Chiara Mannino; Annalisa Greco; Carlo De Lorenzo; Francesco Andreozzi; Maria A Marini; Francesco Perticone; Giorgio Sesti

doi:10.1371/journal.pone.0085483

A fasting insulin-raising allele at IGF1 locus is associated with circulating levels of IGF-1 and insulin sensitivity

PLoS One. 2013 Dec 31;8(12):e85483. doi: 10.1371/journal.pone.0085483. eCollection 2013.

Authors

Gaia Chiara Mannino¹, Annalisa Greco¹, Carlo De Lorenzo¹, Francesco Andreozzi¹, Maria A Marini², Francesco Perticone¹, Giorgio Sesti¹

Affiliations

¹ Department of Medical and Surgical Sciences, University "Magna Graecia" of Catanzaro, Catanzaro, Italy.
² Department of Systems Medicine, University of Rome-Tor Vergata, Rome, Italy.

Abstract

Background: A meta-analysis of genome-wide data reported the discovery of the rs35767 polymorphism near IGF1 with genome-wide significant association with fasting insulin levels. However, it is unclear whether the effects of this polymorphism on fasting insulin are mediated by a reduced insulin sensitivity or impaired insulin clearance. We investigated the effects of the rs35767 polymorphism on circulating IGF-1 levels, insulin sensitivity, and insulin clearance.

Methodology/principal findings: Two samples of adult nondiabetic white Europeans were studied. In sample 1 (n=569), IGF-1 levels were lower in GG genotype carriers compared with A allele carriers (190±77 vs. 218±97 ng/ml, respectively; P=0.007 after adjusting for age, gender, and BMI). Insulin sensitivity assessed by euglycaemic-hyperinsulinemic clamp was lower in GG genotype carriers compared with A allele carriers (8.9±4.1 vs. 10.1±5.1 mg x Kg(-1) free fat mass x min(-1), respectively; P=0.03 after adjusting for age, gender, and BMI). The rs35767 polymorphism did not show significant association with insulin clearance. In sample 2 (n=859), IGF-1 levels were lower in GG genotype carriers compared with A allele carriers (155±60 vs. 164±63 ng/ml, respectively; P=0.02 after adjusting for age, gender, and BMI). Insulin sensitivity, as estimated by the HOMA index, was lower in GG genotype carriers compared with A allele carriers (2.8±2.2 vs. 2.5±1.3, respectively; P=0.03 after adjusting for age, gender, and BMI).

Conclusion/significance: The rs35767 polymorphism near IGF1 was associated with circulating IGF-1 levels, and insulin sensitivity with carriers of the GG genotype exhibiting lower IGF-1 concentrations and insulin sensitivity as compared with subjects carrying the A allele.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Alleles*
Fasting / blood*
Female
Genetic Loci / genetics*
Humans
Insulin / blood*
Insulin Resistance / genetics*
Insulin-Like Growth Factor I / genetics*
Insulin-Like Growth Factor I / metabolism*
Male
Polymorphism, Single Nucleotide

Substances

Insulin
Insulin-Like Growth Factor I

Grants and funding

This work was supported, in part, by the European Community (grant number Medigene-FP7-279171-1) to Giorgio Sesti. No additional external funding was received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.