Aarhus Universitets segl

Evidence from case-control and longitudinal studies supports associations of genetic variation in APOE, CETP, and IL6 with human longevity

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

  • Mette Soerensen, Syddansk Universitet, Danmark
  • Serano Dato, Syddansk Universitet, Danmark
  • Qihua Tan, Syddansk Universitet, Danmark
  • Mikael Thinggaard, Syddansk Universitet, Danmark
  • Rabea Kleindorp, Kiel University, Tyskland
  • Marian Beekman, Leiden University, Holland
  • H Eka D Suchiman, Leiden University, Holland
  • Rune Jacobsen, Syddansk Universitet, Danmark
  • Matt McGue, Syddansk Universitet, Danmark
  • Tinna Stevnsner
  • Vilhelm A Bohr, Danmark
  • Anton J M de Craen, Leiden University, Holland
  • Rudi G J Westendorp, Leiden University, Tyskland
  • Stefan Schreiber, Kiel University, Tyskland
  • P Eline Slagboom, Leiden University, Holland
  • Almut Nebel, Kiel University, Tyskland
  • James W Vaupel, Syddansk Universitet, Danmark
  • Kaare Christensen, Syddansk Universitet, Danmark
  • Lene Christiansen, Syddansk Universitet, Danmark
In this study, we investigated 102 single-nucleotide polymorphisms (SNPs) covering the common genetic variation in 16 genes recurrently regarded as candidates for human longevity: APOE; ACE; CETP; HFE; IL6; IL6R; MTHFR; TGFB1; APOA4; APOC3; SIRTs 1, 3, 6; and HSPAs 1A, 1L, 14. In a case–control study of 1,089 oldest-old (ages 92–93) and 736 middle-aged Danes, the minor allele frequency (MAF) of rs769449 (APOE) was significantly decreased in the oldest-old, while the MAF of rs9923854 (CETP) was significantly enriched. These effects were supported when investigating 1,613 oldest-old (ages 95–110) and 1,104 middle-aged Germans. rs769449 was in modest linkage equilibrium (R 2 = 0.55) with rs429358 of the APOE-ε4 haplotype and adjusting for rs429358 eliminated the association of rs769449, indicating that the association likely reflects the well-known effect of rs429358. Gene-based analysis confirmed the effects of variation in APOE and CETP and furthermore pointed to HSPA14 as a longevity gene. In a longitudinal study with 11 years of follow-up on survival in the oldest-old Danes, only one SNP, rs2069827 (IL6), was borderline significantly associated with survival from age 92 (P-corrected = 0.064). This advantageous effect of the minor allele was supported when investigating a Dutch longitudinal cohort (N = 563) of oldest-old (age 85+). Since rs2069827 was located in a putative transcription factor binding site, quantitative RNA expression studies were conducted. However, no difference in IL6 expression was observed between rs2069827 genotype groups. In conclusion, we here support and expand the evidence suggesting that genetic variation in APOE, CETP, and IL6, and possible HSPA14, is associated with human longevity
TidsskriftAge (Omaha)
Sider (fra-til)487-500
Antal sider13
StatusUdgivet - 2013

Se relationer på Aarhus Universitet Citationsformater

ID: 44368047