title: Polymorphisms associated with type 2 diabetes in familial longevity: The Leiden Longevity Study.
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.
authors.affiliation: Department of Gerontology and Geriatrics , Leiden University Medical Centre, The Netherlands. s.p.mooijaart@lumc.nl
authors.forename: Simon P
authors.initials: SP
authors.lastname: Mooijaart
authors.forename: Diana
authors.initials: D
authors.lastname: van Heemst
authors.forename: Raymond
authors.initials: R
authors.lastname: Noordam
authors.forename: Maarten P
authors.initials: MP
authors.lastname: Rozing
authors.forename: Carolien A
authors.initials: CA
authors.lastname: Wijsman
authors.forename: Anton J M
authors.initials: AJ
authors.lastname: de Craen
authors.forename: Rudi G J
authors.initials: RG
authors.lastname: Westendorp
authors.forename: Marian
authors.initials: M
authors.lastname: Beekman
authors.forename: P Eline
authors.initials: PE
authors.lastname: Slagboom
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics; D000483:Alleles; D001786:Blood Glucose / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D005951:Glucose Tolerance Test; D006801:Humans; D008136:Longevity / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: D001786:Blood Glucose