Research Paper Volume 3, Issue 1 pp 55—62
Polymorphisms associated with type 2 diabetes in familial longevity: The Leiden Longevity Study
- 1 Department of Gerontology and Geriatrics, Leiden University Medical Centre, Leiden, The Netherlands
- 2 Section of Molecular Epidemiology of the Department of Medical Statistics, Leiden University Medical Centre, Leiden, The Netherlands
- 3 The Netherlands Consortium for Healthy Aging, The Netherlands
Received: November 12, 2010 Accepted: December 18, 2010 Published: December 20, 2010https://doi.org/10.18632/aging.100250
How to Cite
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.