• Experimental gerontology · Jul 2014

    Gene-gene interaction between CETP and APOE polymorphisms confers higher risk for hypertriglyceridemia in oldest-old Chinese women.

    • Liang Sun, Caiyou Hu, Chenguang Zheng, Zezhi Huang, Zeping Lv, Jin Huang, Siying Liang, Xiaohong Shi, Xiaoquan Zhu, Huiping Yuan, and Ze Yang.
    • The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, Beijing, China. Electronic address: sunbmu@foxmail.com.
    • Exp. Gerontol. 2014 Jul 1;55:129-33.

    AbstractThe 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.Copyright © 2014 Elsevier Inc. All rights reserved.

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