Abstract
BackgroundThe 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.MethodsWe 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.ResultsOur case-control data indicated that CETP 405V is a longevity risk allele in all genetic models (P additive=0.008; P dominant=0.008, ORdominant=0.673; P recessive=0.017, ORrecessive=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.ConclusionOur 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.
Highlights
The recent increase in world-wide aging has resulted in an unprecedentedly focused on human longevity by health researchers, policymakers and the general public [1]
Bivariate Spearman correlation analysis indicated a decrease of total cholesterol (TC), TG, body mass index (BMI) and waist circumstances (WC) with increased ages in the longevity group (Figure S1)
To understand the genetics and the biological processes involved in aging and longevity is one of the greatest challenges
Summary
The recent increase in world-wide aging has resulted in an unprecedentedly focused on human longevity by health researchers, policymakers and the general public [1]. If a genetic association is discovered in one racial or ethnic background, it is necessary to confirm it in another to achieve worldwide benefit, the confounding from population genetic structure definitely reduce the replication efficiency in case-control studies [5]. According to the specific racial/ethnic genetic background and lifestyle, it is necessary to confirm one previous discovery in different populations, even for the translation and benefit around the world. The associations with even a single polymorphism To this end, we performed an association analysis between CETP I405V and longevity in a Chinese population, as the largest such research conducted in East Asia to date, followed by a metaanalysis of the literature on similar subjects
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