Genetics
CETP I405V fails to replicate as a longevity gene in a large American Caucasian cohort (Biogerontology 2007)
Original title: Lack of replication of genetic associations with human longevity
Researchers attempted to replicate previously published genetic associations with exceptional longevity in 749 American Caucasian long-living individuals, organised into two independent tiers, and 355 American Caucasian controls. They tested six candidate variants, including CETP I405V (rs5882), alongside Klotho, PON1, APOC3, MTP, and APOE. After validating their populations by confirming the well-established APOE association, none of the other tested genes, including CETP I405V, showed association with longevity when carefully tested in this large cohort. The authors conclude that, aside from APOE, previously reported longevity gene associations have not been convincingly reproduced, and larger populations are needed for future case-control studies of extreme longevity.
Original abstract
The exceptional longevity of centenarians is due in part to inherited genetic factors, as deduced from data that show that first degree relatives of centenarians live longer and have reduced overall mortality. In recent years, a number of groups have performed genetic association studies on long-living individuals (LLI) and young controls to identify alleles that are either positively or negatively selected in the centenarian population as consequence of a demographic pressure. Many of the reported studies have shown genetic loci associated with longevity. Of these, with the exception of APOE, none have been convincingly reproduced. We validated our populations by typing the APOE locus. In addition, we used 749 American Caucasian LLI, organized in two independent tiers and 355 American Caucasian controls in the attempt to replicate previously published findings. We tested Klotho (KL)-VS variant (rs952706), Cholesteryl Ester Transfer Protein (CETP) I405V (rs5882), Paraoxonase 1 (PON1) Q192R (rs662), Apolipoprotein C-III (APOC3) -641C/A (rs2542052), Microsomal Transfer Protein (MTP) -493G/T (rs2866164) and apolipoprotein E (APOE) epsilon2 and epsilon4 isoforms, (rs7412 and rs429358) haplotypes respectively. Our results show that, at present, except for APOE, none of the selected genes show association with longevity if carefully tested in a large cohort of LLI and their controls, pointing to the need of larger populations for case-control studies in extreme longevity.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.