Apolipoprotein E gene is related to mortality only in normal weight individuals: The Rotterdam study

Objective To investigate the relationship between the apolipoprotein E (APOE) gene and the risk of mortality in normal weight, overweight and obese individuals. Methods and Results In a population-based study of 7,983 individuals aged 55 years and older, we compared the risks of all-cause and coronary heart disease (CHD) mortality by APOE genotype, both overall and in subgroups defined by body mass index (BMI). We found significant evidence for interaction between APOE and BMI in relation to total cholesterol (p = 0.04) and HDL cholesterol (p < 0.001). Overall, APOE*2 carriers showed a decreased risk of all-cause mortality. Analyses within BMI strata showed a beneficial effect of APOE*2 only in normal weight persons (adjusted hazard ratio (HR) 0.7[95% CI 0.5–0.9]). APOE*2 was not associated with a lower risk of all-cause mortality in overweight or obese persons. The effect of APOE*2 in normal weight individuals tended to be due to the risk of CHD mortality (adjusted HR 0.5 [95% CI 0.2–1.2]). Conclusion The APOE*2 allele confers a lower risk of all-cause mortality only to normal weight individuals

Reduced Physiological Complexity in Robust Elderly Adults with the APOE ε4 Allele

BACKGROUND:It is unclear whether the loss of physiological complexity during the aging process is due to genetic variations. The APOE gene has been studied extensively in regard to its relationship with aging-associated medical illness. We hypothesize that diminished physiological complexity, as measured by heart rate variability, is influenced by polymorphisms in the APOE allele among elderly individuals. METHODOLOGY/PRINCIPAL FINDINGS:A total of 102 robust, non-demented, elderly subjects with normal functions of daily activities participated in this study (97 males and 5 females, aged 79.2+/-4.4 years, range 72-92 years). Among these individuals, the following two APOE genotypes were represented: epsilon4 non-carriers (n = 87, 85.3%) and epsilon4 carriers (n = 15, 14.7%). Multi-scale entropy (MSE), an analysis used in quantifying complexity for nonlinear time series, was employed to analyze heart-rate dynamics. Reduced physiological complexity, as measured by MSE, was significantly associated with the presence of the APOE epsilon4 allele in healthy elderly subjects, as compared to APOE epsilon4 allele non-carriers (24.6+/-5.5 versus 28.9+/-5.2, F = 9.429, p = 0.003, respectively). CONCLUSIONS/SIGNIFICANCE:This finding suggests a role for the APOE gene in the diminished physiological complexity seen in elderly populations

Selection on Alleles Affecting Human Longevity and Late-Life Disease: The Example of Apolipoprotein E

It is often claimed that genes affecting health in old age, such as cardiovascular and Alzheimer diseases, are beyond the reach of natural selection. We show in a simulation study based on known genetic (apolipoprotein E) and non-genetic risk factors (gender, diet, smoking, alcohol, exercise) that, because there is a statistical distribution of ages at which these genes exert their influence on morbidity and mortality, the effects of selection are in fact non-negligible. A gradual increase with each generation of the ε2 and ε3 alleles of the gene at the expense of the ε4 allele was predicted from the model. The ε2 allele frequency was found to increase slightly more rapidly than that for ε3, although there was no statistically significant difference between the two. Our result may explain the recent evolutionary history of the epsilon 2, 3 and 4 alleles of the apolipoprotein E gene and has wider relevance for genes affecting human longevity

Atherosclerosis in 64-year-old women with diabetes mellitus and impaired glucose tolerance

Atherosclerosis in 64-year-old women with diabetes mellitus and impaired glucose tolerance The incidence of obesity and type-2 diabetes (t2D) is rising around the world. T2D is accompanied by an increased risk of macrovascular, atherosclerotic diseases. The timing of the disease process and exact mechanism underlying the association between diabetes and atherosclerotic disease are not known. High-resolution B-mode ultrasound is a non-invasive technique to measure very early atherosclerotic disease as the intima-media thickness (IMT) and to assess occurrence, size and echogenicity of atherosclerotic plaques in superficial arteries such as the carotid arteries. Remodelling, i.e a change in vascular diameter in response to atherosclerosis may also be examined. The overallaim of this thesis was to examine the occurrence of early atherosclerosis in t2D and impaired glucose tolerance (IGT). Our hypothesis was that there is a gradual enlargement of IMT and an increased occurrence of plaques, especially echolucent plaques, with worsening glucose tolerance, accompanied by a remodelling that might be visible already in subjects with IGT. Inorder to summarise current knowledge a systematic reviews were made in order to identify cross-sectional studies using the ultrasound method. The differences between IMT in t2D or IGT and control subjects were calculated. Meta-analysis using random-effects model was used to calculate summary measures. In a cross-sectional study, the entire cohort of 64 years old women in Göteborg were invited to take part in a screening examination. Of these, 2595 participated and underwent anthropometric measurements and an oral glucose tolerance test (OGTT) that was repeated within two weeks. Ultrasound examinations were made in a cohort of women with known (n=99) and new diabetes (n=106), IGT (n=205) and NGT (n=188). In the systematic review of 23 studies we found that t2D was associated with an 0.13 mm increase in IMT compared to controls. There was a considerable heterogeneity between the studies that complicated the interpretation of the meta-analysis. This difference can be interpreted as if the diabetic patients were ten years older than the control group and that they had an elevated risk for stroke and myocardial infarction. In patients with IGT, the increase in IMT was about 25% of that observed in diabetes. The screening examination showed that 10% of the women had diabetes of whom half were newly detected. Without repeated OGTTs 37% of the new diabetes would have been missed. The women with t2D had larger IMT and plaqueareas compared to women in IGT and NGT groups. The plaques were most frequenty echolucent. In the IGT group, no increase in atherosclerosis was observed, but the result was within the confidenceinterval of the meta-analysis, indicating that IGT is associated with a small increase in IMT in the CCA (0.03mm). Carotid vascular remodelling with enlargement in IMT and lumen diameter had however occurred already in the women with new t2D. This remodelling process was seen only in women with atherosclerotic plaques and was not associated to t2D per se. In conclusion, already in screening detected diabetes sub-clinical atherosclerosis with IMT enlargement and occurrence of plaque with vascular remodelling are observed, indicating that a powerful intervention must be initiated in such cases