title: Gene-gene interaction between CETP and APOE polymorphisms confers higher risk for hypertriglyceridemia in oldest-old Chinese women.
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.
authors.affiliation: The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, Beijing, China. Electronic address: sunbmu@foxmail.com.
authors.forename: Liang
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Neurology, Jiangbin Hospital, Nanning, Guangxi, China.
authors.forename: Caiyou
authors.initials: C
authors.lastname: Hu
authors.affiliation: Department of Cardiothoracic Surgery, Guangxi Maternal and Child Health Hospital, Nanning, Guangxi, China.
authors.forename: Chenguang
authors.initials: C
authors.lastname: Zheng
authors.affiliation: Yongfu Committee of the Chinese People's Political Consultative Conference, Yongfu, Guangxi, China.
authors.forename: Zezhi
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Neurology, Jiangbin Hospital, Nanning, Guangxi, China.
authors.forename: Zeping
authors.initials: Z
authors.lastname: Lv
authors.affiliation: The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, Beijing, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Huang
authors.affiliation: The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, Beijing, China.
authors.forename: Siying
authors.initials: S
authors.lastname: Liang
authors.affiliation: The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, Beijing, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Shi
authors.affiliation: The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, Beijing, China.
authors.forename: Xiaoquan
authors.initials: X
authors.lastname: Zhu
authors.affiliation: The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, Beijing, China.
authors.forename: Huiping
authors.initials: H
authors.lastname: Yuan
authors.affiliation: The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, Beijing, China. Electronic address: yang_ze@sina.com.
authors.forename: Ze
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D001057:Apolipoproteins E / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000235:genetics*; D008055:Lipids / Q000097:blood; D008136:Longevity / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D055815:Young Adult
chemical_list: D001057:Apolipoproteins E; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008055:Lipids
keywords: APOE; CETP; Gene–gene interaction; Hypertriglyceridemia; Longevity