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Association of APOE ε4 genotype and lifestyle with cognitive function among Chinese adults aged 80 years and older: A cross-sectional study.
Jin, X, He, W, Zhang, Y, Gong, E, Niu, Z, Ji, J, Li, Y, Zeng, Y, Yan, LL
PLoS medicine. 2021;(6):e1003597
Abstract
BACKGROUND Apolipoprotein E (APOE) ε4 is the single most important genetic risk factor for cognitive impairment and Alzheimer disease (AD), while lifestyle factors such as smoking, drinking, diet, and physical activity also have impact on cognition. The goal of the study is to investigate whether the association between lifestyle and cognition varies by APOE genotype among the oldest old. METHODS AND FINDINGS We used the cross-sectional data including 6,160 oldest old (aged 80 years old or older) from the genetic substudy of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) which is a national wide cohort study that began in 1998 with follow-up surveys every 2-3 years. Cognitive impairment was defined as a Mini-Mental State Examination (MMSE) score less than 18. Healthy lifestyle profile was classified into 3 groups by a composite measure including smoking, alcohol consumption, dietary pattern, physical activity, and body weight. APOE genotype was categorized as APOE ε4 carriers versus noncarriers. We examined the associations of cognitive impairment with lifestyle profile and APOE genotype using multivariable logistic regressions, controlling for age, sex, education, marital status, residence, disability, and numbers of chronic conditions. The mean age of our study sample was 90.1 (standard deviation [SD], 7.2) years (range 80-113); 57.6% were women, and 17.5% were APOE ε4 carriers. The mean MMSE score was 21.4 (SD: 9.2), and 25.0% had cognitive impairment. Compared with those with an unhealthy lifestyle, participants with intermediate and healthy lifestyle profiles were associated with 28% (95% confidence interval [CI]: 16%-38%, P < 0.001) and 55% (95% CI: 44%-64%, P < 0.001) lower adjusted odds of cognitive impairment. Carrying the APOE ε4 allele was associated with 17% higher odds (95% CI: 1%-31%, P = 0.042) of being cognitively impaired in the adjusted model. The association between lifestyle profiles and cognitive function did not vary significantly by APOE ε4 genotype (noncarriers: 0.47 [0.37-0.60] healthy versus unhealthy; carriers: 0.33 [0.18-0.58], P for interaction = 0.30). The main limitation was the lifestyle measurements were self-reported and were nonspecific. Generalizability of the findings is another limitation because the study sample was from the oldest old in China, with unique characteristics such as low body weight compared to populations in high-income countries. CONCLUSIONS In this study, we observed that healthier lifestyle was associated with better cognitive function among the oldest old regardless of APOE genotype. Our findings may inform the cognitive outlook for those oldest old with high genetic risk of cognitive impairment.
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High Apolipoprotein E Levels Predict Adverse Limb Events in Patients with Peripheral Artery Disease Due to Peripheral Artery Disease Undergoing Endovascular Treatment and On-Statin Treatment.
Fukase, T, Dohi, T, Kato, Y, Chikata, Y, Takahashi, N, Endo, H, Doi, S, Nishiyama, H, Okai, I, Iwata, H, et al
International heart journal. 2021;(4):872-878
Abstract
Little is known about the association between limb prognosis in peripheral artery disease and apolipoprotein E (apoE). We evaluated the long-term impact of apoE on adverse limb events in patients with intermittent claudication receiving statin treatment.A total of 218 consecutive patients (mean age, 73 ± 8 years; 81% men) with intermittent claudication who underwent their first intervention between 2009 and 2020 were included in this study. All patients had achieved LDL-C < 100 mg/dL on statin treatment and were divided into two groups based on the apoE value (≥ 4.7 or < 4.7 mg/dL). We evaluated the incidence of major adverse limb events (MALEs), including vessel revascularization and limb ischemia development.A total of 39 and 179 patients were allocated to the higher and lower apoE groups, respectively. Compared to the lower apoE group, the higher apoE group had a significantly higher total cholesterol level, triglyceride level, and non-high-density lipoprotein cholesterol level. During the median follow-up period of 3.6 years, 30 patients (13.8%) developed MALEs. Kaplan-Meier analysis revealed that the cumulative incidence of MALEs in the higher apoE group was significantly higher than that in the lower apoE group (44.0% versus 21.6%, log-rank test, P = 0.002). During multivariable Cox hazard analysis, higher apoE level (≥ 4.7 mg/dL) (hazard ratio, 2.61; 95% confidence interval, 1.18-5.70, P = 0.019) was the only strong independent predictor of MALEs.ApoE levels could be a strong predictor and residual risk for long-term limb prognosis in patients with intermittent claudication and achieving LDL-C < 100 mg/dL with statin treatment.
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VLDL (Very-Low-Density Lipoprotein)-Apo E (Apolipoprotein E) May Influence Lp(a) (Lipoprotein [a]) Synthesis or Assembly.
Croyal, M, Blanchard, V, Ouguerram, K, Chétiveaux, M, Cabioch, L, Moyon, T, Billon-Crossouard, S, Aguesse, A, Bernardeau, K, Le May, C, et al
Arteriosclerosis, thrombosis, and vascular biology. 2020;(3):819-829
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Abstract
OBJECTIVE To clarify the association between PCSK9 (proprotein convertase subtilisin/kexin type 9) and Lp(a) (lipoprotein [a]), we studied Lp(a) kinetics in patients with loss-of-function and gain-of-function PCSK9 mutations and in patients in whom extended-release niacin reduced Lp(a) and PCSK9 concentrations. Approach and Results: Six healthy controls, 9 heterozygous patients with familial hypercholesterolemia (5 with low-density lipoprotein receptor [LDLR] mutations and 4 with PCSK9 gain-of-function mutations) and 3 patients with heterozygous dominant-negative PCSK9 loss-of-function mutations were included in the preliminary study. Eight patients were enrolled in a second study assessing the effects of 2 g/day extended-release niacin. Apolipoprotein kinetics in VLDL (very-low-density lipoprotein), LDL (low-density lipoprotein), and Lp(a) were studied using stable isotope techniques. Plasma Lp(a) concentrations were increased in PCSK9-gain-of-function and familial hypercholesterolemia-LDLR groups compared with controls and PCSK9-loss-of-function groups (14±12 versus 5±4 mg/dL; P=0.04), but no change was observed in Lp(a) fractional catabolic rate. Subjects with PCSK9-loss-of-function mutations displayed reduced apoE (apolipoprotein E) concentrations associated with a VLDL-apoE absolute production rate reduction. Lp(a) and VLDL-apoE absolute production rates were correlated (r=0.50; P<0.05). ApoE-to-apolipoprotein (a) molar ratios in Lp(a) increased with plasma Lp(a) (r=0.96; P<0.001) but not with PCSK9 levels. Extended-release niacin-induced reductions in Lp(a) and VLDL-apoE absolute production rate were correlated (r=0.83; P=0.015). In contrast, PCSK9 reduction (-35%; P=0.008) was only correlated with that of VLDL-apoE absolute production rate (r=0.79; P=0.028). CONCLUSIONS VLDL-apoE production could determine Lp(a) production and/or assembly. As PCSK9 inhibitors reduce plasma apoE and Lp(a) concentrations, apoE could be the link between PCSK9 and Lp(a).
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OxLDL plasma levels in patients with Alzheimer's disease.
Grossi, MF, Carvalho, MDG, Silveira, JN, Gonçalves, GS, Gomes, KB, Bicalho, MA, Silva, IFO
Arquivos de neuro-psiquiatria. 2018;(4):241-246
Abstract
OBJECTIVE The objective of this study was to characterize the conventional lipid profile, oxLDL levels and ApoE polymorphism in patients with Alzheimer's disease (AD) and in elderly individuals without cognitive impairment. METHODS Eighty elderly individuals were selected and the levels of oxLDL were determined using the ELISA kit, and ApoE gene polymorphism was investigated using polymerase chain reaction-restriction fragment length polymorphism. RESULTS Significantly reduced levels of oxLDL were observed in patients with AD compared to the control group. A higher frequency of the ApoE ε4 allele was observed in patients with AD compared to controls. No difference was observed for total cholesterol, HDL-C, and LDL-C levels between the two groups, while triglyceride levels were higher in controls compared with patients with AD. CONCLUSION The data analyzed together did not reveal significant differences in lipid profiles, including oxLDL levels. However, the importance of lipid changes in the genesis of the disease cannot be ruled out. Nevertheless, the ApoE ε4 allele was significantly more frequent in patients with Alzheimer's dementia in agreement with previous findings in the literature, but this genetic component did not change the levels of oxLDL.
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High-density lipoprotein cholesterol, apolipoprotein E and atherogenic index of plasma are associated with risk of chronic kidney disease.
Smajić, J, Hasić, S, Rašić, S
Medicinski glasnik : official publication of the Medical Association of Zenica-Doboj Canton, Bosnia and Herzegovina. 2018;(2):115-121
Abstract
Aim To investigate the association of parameters of lipid profile and estimated glomerular filtration rate (eGFR) p<60 ml/min/1.73m2 calculated by the Modification of Diet in Renal Disease (MDRD) in non-dialysis kidney patients. Methods The observational, case-control study enrolled patients (n=117) recruited from the Nephrological Counselling Centre of the University Clinical Centre Sarajevo and divided into two groups: group 1 eGFR (15-59 mL/min/1.73 m2 ), and group 2 (control) eGFR ≥ 60 mL/min/1.73 m2 . Concentration of lipids, lipoproteins and apolipoproteins was measured, and atherogenic index of plasma (AIP; log(TG/HDLc)) was calculated. Results High density lipoprotein cholesterol (HDLc) and apolipoprotein E (APOE) concentrations in serum were reduced [(1.02 (0.94-1.29) vs 1.15 (1.1-1.4) mmol/L; p=0.009 and 0.035 (0.026-0.04) vs 0.041 (0.034-0.05) g/L; p=0.002, respectively)], while AIP was higher in group 1 than in group 2 (0.19±0.03 vs 0.09±0.04; p=0.013). Values less than 1.09 mmol/L and 0.038 g/L for HDLc and APOE, or higher than 0.165 for AIP (p< 0.05) were associated with the eGFR below 60 ml/min/1.73 m2. The age [OR = 1.1; 95% CI (1.05-1.17)] and AIP [OR = 8.7; 95% CI (1.18- 65.0)] were independent positive predictors, while APOE was a negative predictor of eGFR reduction rate (OR=0.01; 95% CI (0.001-0.033; p<0.001). Conclusion Changes in parameters such as HDLc, APOE and AIP are associated with CKD. The study results imply the need of the AIP calculation as routine laboratory work due to its role along with the age and APOE in the prediction of renal function decline.
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A 6-Month Follow-Up Study of the Relation between Apolipoprotein E Gene Polymorphism and Major Adverse Cardiovascular Events in Patients with Acute Coronary Syndrome.
Xia, J, Hu, S, Yin, C, Xu, D
Cardiology. 2018;(3):187-193
Abstract
OBJECTIVES This study aimed to investigate the relation between ApoE gene polymorphisms and major adverse cardiovascular events (MACE) in patients with acute coronary syndrome (ACS) during a 6-month follow-up. METHODS From October 2016 to July 2017, 211 patients were admitted to a cardiology clinic with a diagnosis of ACS. Blood samples were obtained from all patients on the first day. The primary end point was a 6-month incidence of MACE. ApoE gene polymorphism was genotyped by real-time PCR using TaqMan® SNP Genotyping Assay. RESULTS The patients with the E4 allele were associated with higher low-density lipoprotein (LDL) cholesterol and total cholesterol (TC) levels compared with the patients without the E4 allele (p = 0001 and p = 0.001). The patients with the E4 allele were associated with a higher rate of MACE compared with the patients without the E4 allele (ApoE4 allele(+) 23.1% vs. ApoE4 allele(-) 9.3%; p = 0.03). Multivariable analysis suggested that E4 allele carriers showed an 85% risk increment of 6-month MACE (odds ratio 2.48, 95% confidence interval 2.37-5.95; p = 0.01). CONCLUSIONS The trial shows that E4 allele carriers were correlated with not only higher LDL cholesterol and TC levels, but also with a higher incidence of MACE during a 6-month follow-up.
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Association between Apolipoprotein E Variants and Obesity-Related Traits in Mexican School Children.
Rodríguez-Carmona, Y, Pérez-Rodríguez, M, Gámez-Valdez, E, López-Alavez, FJ, Hernández-Armenta, CI, Vega-Monter, N, Leyva-García, G, Monge-Cázares, T, Barrera Valencia, D, Balderas Monroy, M, et al
Journal of nutrigenetics and nutrigenomics. 2014;(4-6):243-51
Abstract
BACKGROUND/AIM: Genetic variation in apolipoprotein E (ApoE) has a key role in lipid metabolism. However, its contribution to the amount and distribution of body fat is under investigation. The aim of this study was to analyze the association between genetic variation in ApoE and obesity-related traits in Mexican school children. MATERIAL AND METHODS Anthropometric, body composition and physical activity measures were conducted using standard methods in 300 children (177 girls/123 boys) who fulfilled the inclusion criteria. DNA was isolated from saliva. ApoE genotypes were analyzed by allelic discrimination. The association between variation in ApoE and anthropometric and body composition measures was investigated using the General Linear Model. RESULTS The mean±SD values for age, body mass index (BMI) and waist circumference (WC) were 9.05±0.80 years, 19.01±3.83 and 67.98±10.97 cm, respectively. Approximately 46% of the participants were overweight or obese. A significant association between ApoE isoforms and WC was found after controlling for age, sex and the percentage of physical activity (p=0.025). Significant main effects were found for vigorous physical activity and light physical activity influencing the adiposity-related BMI (p<0.001) and WC (p=0.044), respectively. CONCLUSIONS Variation in ApoE and physical activity intensity were associated with adiposity-related phenotypes in Mexican school children.