Human longevity and variation in GH/IGF-1/insulin signaling, DNA damage signaling and repair and pro/antioxidant pathway genes: cross sectional and longitudinal studies

Mette Soerensen, Serena Dato, Qihua Tan, Mikael Thinggaard, Rabea Kleindorp, Marian Beekman, Rune Jacobsen, H Eka D Suchiman, Anton J M de Craen, Rudi G J Westendorp, Stefan Schreiber, Tinna Stevnsner, Vilhelm A Bohr, P Eline Slagboom, Almut Nebel, James W. Vaupel, Kaare Christensen, Matt McGue, Lene Christiansen

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Abstract

Here we explore association with human longevity of common genetic variation in three major candidate pathways: GH/IGF-1/insulin signaling, DNA damage signaling and repair and pro/antioxidants by investigating 1273 tagging SNPs in 148 genes composing these pathways. In a case-control study of 1089 oldest-old (age 92-93) and 736 middle-aged Danes we found 1 pro/antioxidant SNP (rs1002149 (GSR)), 5 GH/IGF-1/INS SNPs (rs1207362 (KL), rs2267723 (GHRHR), rs3842755 (INS), rs572169 (GHSR), rs9456497 (IGF2R)) and 5 DNA repair SNPs (rs11571461 (RAD52), rs13251813 (WRN), rs1805329 (RAD23B), rs2953983 (POLB), rs3211994 (NTLH1)) to be associated with longevity after correction for multiple testing. In a longitudinal study with 11 years of follow-up on survival in the oldest-old Danes we found 2 pro/antioxidant SNPs (rs10047589 (TNXRD1), rs207444 (XDH)), 1 GH/IGF-1/INS SNP (rs26802 (GHRL)) and 3 DNA repair SNPs (rs13320360 (MLH1), rs2509049 (H2AFX) and rs705649 (XRCC5)) to be associated with mortality in late life after correction for multiple testing. When examining the 11 SNPs from the case-control study in the longitudinal data, rs3842755 (INS), rs13251813 (WRN) and rs3211994 (NTHL1) demonstrated the same directions of effect (p
OriginalsprogEngelsk
TidsskriftExperimental Gerontology
Vol/bind47
Nummer5
Sider (fra-til)379-387
Antal sider9
ISSN0531-5565
DOI
StatusUdgivet - maj 2012

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