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Research Paper|Volume 3, Issue 1|pp 55—62

Polymorphisms associated with type 2 diabetes in familial longevity: The Leiden Longevity Study

Simon P. Mooijaart1, Diana van Heemst1, Raymond Noordam1, Maarten P. Rozing1, Carolien A. Wijsman1, Anton J.M. de Craen1, Rudi G.J. Westendorp1,3, Marian Beekman2, Eline P. Slagboom2,3
  • 1Department of Gerontology and Geriatrics, Leiden University Medical Centre, Leiden, The Netherlands
  • 2Section of Molecular Epidemiology of the Department of Medical Statistics, Leiden University Medical Centre, Leiden, The Netherlands
  • 3The Netherlands Consortium for Healthy Aging, The Netherlands
Received: November 12, 2010Accepted: December 18, 2010Published: December 20, 2010
https://doi.org/10.18632/aging.100250

Copyright: © 2010 Mooijaart et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Human longevity is in part genetically determined, and the insulin/IGF-1 signal transduction (IIS) pathway has consistently been implicated. In humans, type 2 diabetes is a frequent disease that results from loss of glucose homeostasis and for which new candidate polymorphisms now rapidly emerge from genome wide association studies.

In the Leiden Longevity Study (n=2415), the offspring of long lived siblings (“offspring”) who are genetically enriched for longevity were shown to have a more beneficial metabolic profile compared to their environmentally matched partners (“controls”), including better glucose tolerance. We tested whether the “offspring” carry a lower burden of diabetes risk alleles. Fifteen polymorphisms derived from genome wide association (GWA) scans in type 2 diabetes were tested for association with parameters of glucose metabolism in offspring and controls, and burden of risk alleles was compared between offspring and controls.

Among all participants, a higher number of type 2 diabetes risk alleles associated with a higher prevalence of diabetes (P=0.011) and higher serum concentration of glucose (P<0.016) but not insulin (P=0.450). None of the polymorphisms differed in frequency between the offspring and controls (all P>0.05), nor did the mean total number of risk alleles (P=0.977). The association between polymorphisms and glucose levels did not differ between controls and offspring (Pinteraction=0.523).

The better glucose tolerance of the “offspring” is not explained by a lower burden of type 2 diabetes risk alleles, suggesting that specific mechanisms determining longevity exist.