1.
Genetic Moderators of the Impact of Physical Activity on Depressive Symptoms.
Dotson, VM, Hsu, FC, Langaee, TY, McDonough, CW, King, AC, Cohen, RA, Newman, AB, Kritchevsky, SB, Myers, V, Manini, TM, et al
The Journal of frailty & aging. 2016;(1):6-14
Abstract
BACKGROUND Converging evidence suggests that physical activity is an effective intervention for both clinical depression and sub-threshold depressive symptoms; however, findings are not always consistent. These mixed results might reflect heterogeneity in response to physical activity, with some subgroups of individuals responding positively, but not others. OBJECTIVES 1) To examine the impact of genetic variation and sex on changes in depressive symptoms in older adults after a physical activity (PA) intervention, and 2) to determine if PA differentially improves particular symptom dimensions of depression. DESIGN Randomized controlled trial. SETTING Four field centers (Cooper Institute, Stanford University, University of Pittsburgh, and Wake Forest University). PARTICIPANTS 396 community-dwelling adults aged 70-89 years who participated in the Lifestyle Interventions and Independence for Elders Pilot Study (LIFE-P). INTERVENTION 12-month PA intervention compared to an education control. MEASUREMENTS Polymorphisms in the serotonin transporter (5-HTT), brain-derived neurotrophic factor (BDNF), and apolipoprotein E (APOE) genes; 12-month change in the Center for Epidemiologic Studies Depression Scale total score, as well as scores on the depressed affect, somatic symptoms, and lack of positive affect subscales. RESULTS Men randomized to the PA arm showed the greatest decreases in somatic symptoms, with a preferential benefit in male carriers of the BDNF Met allele. Symptoms of lack of positive affect decreased more in men compared to women, particularly in those possessing the 5-HTT L allele, but the effect did not differ by intervention arm. APOE status did not affect change in depressive symptoms. CONCLUSIONS Results of this study suggest that the impact of PA on depressive symptoms varies by genotype and sex, and that PA may mitigate somatic symptoms of depression more than other symptoms. The results suggest that a targeted approach to recommending PA therapy for treatment of depression is viable.
2.
Obesity favors apolipoprotein E- and C-III-containing high density lipoprotein subfractions associated with risk of heart disease.
Talayero, B, Wang, L, Furtado, J, Carey, VJ, Bray, GA, Sacks, FM
Journal of lipid research. 2014;(10):2167-77
Abstract
Human HDLs have highly heterogeneous composition. Plasma concentrations of HDL with apoC-III and of apoE in HDL predict higher incidence of coronary heart disease (CHD). The concentrations of HDL-apoA-I containing apoE, apoC-III, or both and their distribution across HDL sizes are unknown. We studied 20 normal weight and 20 obese subjects matched by age, gender, and race. Plasma HDL was separated by sequential immunoaffinity chromatography (anti-apoA-I, anti-apoC-III, anti-apoE), followed by nondenaturing-gel electrophoresis. Mean HDL-cholesterol concentrations in normal weight and obese subjects were 65 and 50 mg/dl (P = 0.009), and total apoA-I concentrations were 119 and 118 mg/dl, respectively. HDL without apoE or apoC-III was the most prevalent HDL type representing 89% of apoA-I concentration in normal weight and 77% in obese (P = 0.01) individuals; HDL with apoE-only was 5% versus 8% (P = 0.1); HDL with apoC-III-only was 4% versus 10% (P = 0.009); and HDL with apoE and apoC-III was 1.5% versus 4.6% (P = 0.004). Concentrations of apoE and apoC-III in HDL were 1.5-2× higher in obese subjects (P ≤ 0.004). HDL with apoE or apoC-III occurred in all sizes among groups. Obese subjects had higher prevalence of HDL containing apoE or apoC-III, subfractions associated with CHD, whereas normal weight subjects had higher prevalence of HDL without apoE or apoC-III, subfractions with protective association against CHD.
3.
Apolipoprotein-E polymorphism and response to pravastatin in men with coronary artery disease (REGRESS).
Maitland-van der Zee, AH, Jukema, JW, Zwinderman, AH, Hallman, DM, De Boer, A, Kastelein, JJ, De Knijff, P
Acta cardiologica. 2006;(3):327-31
Abstract
OBJECTIVE [corrected] The influence ofApoE polymorphism on the efficacy of statins in lowering plasma lipids and lipoproteins and improving angiographic parameters was assessed. METHODS ApoE genotypes were studied in a group (n = 815) of well-characterised male coronary artery disease (CAD) patients who participated in the lipid-lowering regression study 'Regression Growth Evaluation Statin Study (REGRESS)'. RESULTS There was a significant interaction between treatment (placebo/pravastatin) and APOE genotype when lipid levels were considered, APOE2 + carriers exhibited the largest improvement of HDL levels (+0.15 mmol/l) and LDL/HDL ratios (-0.60) compared with APOE3 + (+ 0.06 mmol/l, -0.043, respectively) and APOE4 + carriers (+ 0.07 mmol/l, -0.040). In contrast,APOE2 + allele carriers had the least effect in terms of angiographic parameters, although the difference was not statistically significant. CONCLUSIONS The effects of statins in subjects with different ApoE genotypes were different with regard to the lipoprotein profile, but not with regard to angiographic parameters.
4.
Cholesterol and APOE genotype interact to influence Alzheimer disease progression.
Evans, RM, Hui, S, Perkins, A, Lahiri, DK, Poirier, J, Farlow, MR
Neurology. 2004;(10):1869-71
Abstract
In this retrospective analysis of 443 Alzheimer disease (AD) patients from a 30-week tacrine trial, change in Alzheimer's Disease Assessment Scale score from baseline to final value was significantly associated with a total serum cholesterol/APOE genotype interaction. Disease progression in the no-APOE epsilon4 allele/high-cholesterol subgroup was greater than in the normal-cholesterol subgroups with or without epsilon4. Cholesterol levels and APOE genotype may interact to affect AD progression. The results are consistent with preclinical data on cholesterol's effects in AD.