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Research Paper|Volume 10, Issue 2|pp 178—196

Genes associated with Type 2 Diabetes and vascular complications

Alberto Montesanto1, Anna Rita Bonfigli2, Paolina Crocco1, Paolo Garagnani3,4, Maria De Luca5, Massimo Boemi6, Elena Marasco3, Chiara Pirazzini3, Cristina Giuliani3, Claudio Franceschi7, Giuseppe Passarino1, Roberto Testa8, Fabiola Olivieri9,10, Giuseppina Rose1
  • 1Department of Biology, Ecology and Earth Sciences, University of Calabria, Rende, Italy
  • 2Scientific Direction, INRCA-IRCCS National Institute, Ancona, Italy
  • 3Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum, University of Bologna, Bologna, Italy
  • 4Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet at Huddinge University Hospital, Stockholm, Sweden
  • 5Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL 35294, USA
  • 6Diabetology Unit, INRCA-IRCCS National Institute, Ancona, Italy
  • 7IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy and Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum-University of Bologna, Bologna, Italy
  • 8Clinical Laboratory and Molecular Diagnostics, INRCA-IRCCS National Institute, Ancona, Italy
  • 9Department of Clinical and Molecular Sciences, DISCLIMO, Università Politecnica delle Marche, Ancona, Italy
  • 10Center of Clinical Pathology and Innovative Therapy, National Institute INRCA-IRCCS, Ancona, Italy

* * Equal contribution

Received: November 17, 2017Accepted: January 30, 2018Published: February 4, 2018
https://doi.org/10.18632/aging.101375

Copyright: © 2018 Montesanto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Type 2 Diabetes (T2D) is a chronic disease associated with a number of micro- and macrovascular complications that increase the morbidity and mortality of patients. The risk of diabetic complications has a strong genetic component. To this end, we sought to evaluate the association of 40 single nucleotide polymorphisms (SNPs) in 21 candidate genes with T2D and its vascular complications in 503 T2D patients and 580 healthy controls. The genes were chosen because previously reported to be associated with T2D complications and/or with the aging process. We replicated the association of T2D risk with IGF2BP rs4402960 and detected novel associations with TERT rs2735940 and rs2736098. The addition of these SNPs to a model including traditional risk factors slightly improved risk prediction. After stratification of patients according to the presence/absence of vascular complications, we found significant associations of variants in the CAT, FTO, and UCP1 genes with diabetic retinopathy and nephropathy. Additionally, a variant in the ADIPOQ gene was found associated with macrovascular complications. Notably, these genes are involved in some way in mitochondrial biology and reactive oxygen species regulation. Hence, our findings strongly suggest a potential link between mitochondrial oxidative homeostasis and individual predisposition to diabetic vascular complications.