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, The Danish Aging Research Center, Epidemiology, Institute of Public Health, University of Southern Denmark, Danmark
  • Serano Dato, The Danish Aging Research Center, Epidemiology, Institute of Public Health, University of Southern Denmark, Danmark
  • Qihua Tan, The Danish Aging Research Center, Epidemiology, Institute of Public Health, University of Southern Denmark, Danmark
  • Mikael Thinggaard, The Danish Aging Research Center, Epidemiology, Institute of Public Health, University of Southern Denmark, Danmark
  • Rabea Kleindorp, Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein and Christian-Albrechts-University, Tyskland
  • Marian Beekman, Department of Molecular Epidemiology, Leiden University Medical Center, Holland
  • H Eka D Suchiman, Department of Molecular Epidemiology, Leiden University Medical Center, Holland
  • Rune Jacobsen, The Danish Aging Research Center, Epidemiology, Institute of Public Health, University of Southern Denmark, Danmark
  • Matt McGue, The Danish Aging Research Center, Epidemiology, Institute of Public Health, University of Southern Denmark, Danmark
  • Tinna Stevnsner
  • Vilhelm A Bohr, Danmark
  • Anton J M de Craen, Department of Gerontology and Geriatrics, Leiden University Medical Center, Holland
  • Rudi G J Westendorp, Department of Gerontology and Geriatrics, Leiden University Medical Center, Tyskland
  • Stefan Schreiber, Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein and Christian-Albrechts-University, Tyskland
  • P Eline Slagboom, Department of Molecular Epidemiology, Leiden University Medical Center, Holland
  • Almut Nebel, Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein and Christian-Albrechts-University, Tyskland
  • James W Vaupel, The Danish Aging Research Center, Epidemiology, Institute of Public Health, University of Southern Denmark, Danmark
  • Kaare Christensen, The Danish Aging Research Center, Epidemiology, Institut of Public Health, University of Southern Denmark, Danmark
  • Lene Christiansen, The Danish Aging Research Center, Epidemiology, Institut of Public Health, University of Southern Denmark, 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
OriginalsprogEngelsk
TidsskriftAge (Omaha)
Vol/bind35
Nummer2
Sider (fra-til)487-500
Antal sider13
ISSN0161-9152
DOI
StatusUdgivet - 2013

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