Genetics
CETP and APOE variants interact to raise hypertriglyceridemia risk in oldest-old Chinese women (Exp Gerontol 2014)
Original title: Gene-gene interaction between CETP and APOE polymorphisms confers higher risk for hypertriglyceridemia in oldest-old Chinese women
Researchers analysed the CETPV (rs5882) and APOE4 variants in 372 oldest-old Chinese women aged 80 to 109 and 340 younger controls, to evaluate their individual and combined contributions to dyslipidaemia risk in extreme old age. Only APOE4 was associated with reduced longevity and with high cholesterol and mixed dyslipidaemia, while CETPV was independently associated with hypertriglyceridemia regardless of APOE4, age, BMI, alcohol use, and standard lipid levels. Statistical interaction analyses confirmed a significant CETP-APOE interaction for hypertriglyceridemia risk, with more than four-fold higher unadjusted odds in women carrying both CETPV and APOE*4 than those carrying neither (odds ratio 4.36, P less than 0.001).
Original abstract
The knowledge of dyslipidemia and its genetic contributors in oldest-old subjects is limited; in addition, the majority of oldest-old subjects are females. Evidence has accumulated that multiple genetic factors play important roles in determining susceptibility to dyslipidemia and extended life span. Cholesterol ester transfer protein (CETP) and apolipoprotein E (APOE) are two plausible candidate genes for human longevity owing to their functionally related modulation of circulating lipid homeostasis; however, few studies have considered their interplay. In this study, we analyzed the distribution of CETP*V (rs5882) and APOE*4 (rs429358 and rs7412) in 372 oldest-old Chinese women (aged 80-109) and 340 controls (aged 20-58). In addition to replicating the association of longevity, our main goal was to evaluate the contribution of CETP*V, APOE*4 and CETP*APOE interaction to the risk of dyslipidemia. Only APOE*4 conferred a risk against longevity and was associated with high-cholesterol (hTC) and mixed dyslipidemia for oldest-old females. Moreover, CETP*V was found to be associated with hypertriglyceridemia (hTG) independently from APOE*4, age, BMI, alcohol drinking, TC, TG, HDL-c, and LDL-c. The stratification test, multivariable-adjusted logistic regression, and nonparametric MDR analysis all suggested a significant CETP*APOE interaction associated with hTG. The unadjusted odds for hTG were more than 4-fold in subjects with CETP*V and APOE*4 than those without either (OR=4.36, P<0.001). These results provide evidence of strong independent associations between hTG and CETP*V in oldest-old Chinese females, and APOE*4, as an independently non-significant variant, might interact with CETP*V resulting in an increased risk for hTG.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.