Apolipoprotein E polymorphism in cerebrovascular & coronary heart diseases

Department of Environmental Sciences, Bharathiar University, Coimbatore, India.
The Indian Journal of Medical Research (Impact Factor: 1.4). 10/2010; 132(10):363-78.
Source: PubMed


The role of apolipoprotein E (apo E) in lipid metabolism and cholesterol transport is well established. About 14 per cent of the variation in plasma cholesterol levels is attributed to polymorphisms in APO E gene (APO E). APO E consists of three common alleles, designated as ε2, ε3 and ε4 which code for E2, E3 and E4 proteins respectively resulting in three homozygous (E2/E2, E3/E3, E4/E4) and three heterozygous (E3/E2, E4/E2 and E4/E3) phenotypes. Different populations studied worldwide inherit variable frequencies of the APO E alleles and genotypes, with the most frequent allele being ε3.The ε4 allele has been consistently shown to be associated with Alzheimer's disease, coronary heart disease and cerebrovascular disorders. In this review, we have discussed the role of APO E polymorphisms in cerebrovascular and coronary heart diseases. The status of APO E polymorphisms and their disease associations in Asian Indians besides, other populations has also been discussed. Further, studies elucidating the pathophysiology of apo E deficiency conducted in knock-out mice have been reviewed.

  • Source
    • "Taken together, these findings establish the importance of APOE genotype in AD and appear to provide a compelling case for the amyloid hypothesis. The ε4 allele is associated not only with increased AD risk, but also increased plasma levels of cholesterol (Ehnholm et al., 1986; Boerwinkle et al., 1987; Fenili and McLaurin, 2005), as well as higher rates of cardiovascular disease (Song et al., 2004; Anoop et al., 2010) and stroke (Kalaria, 2001; Szolnoki and Melegh, 2006). Furthermore, the ε4 allele amplifies AD risk associated with diabetes. "
    [Show abstract] [Hide abstract]
    ABSTRACT: As of 2010, the worldwide economic impact of dementia was estimated at $604 billion USD; and without discovery of a cure or effective interventions to delay disease progression, dementia’s annual global economic impact is expected to surpass $1 trillion USD as early as 2030. Alzheimer’s disease (AD) is the leading cause of dementia accounting for over 75% of all cases. Toxic accumulation of amyloid beta (Aβ), either by overproduction or some clearance failure, is thought to be an underlying mechanism of the neuronal cell death characteristic of AD—though this amyloid hypothesis has been increasingly challenged in recent years. A compelling alternative hypothesis points to chronic neuroinflammation as a common root in late-life degenerative diseases including AD. Apolipoprotein-E (APOE) genotype is the strongest genetic risk factor for AD: APOE-ε4 is proinflammatory and individuals with this genotype accumulate more Aβ, are at high risk of developing AD, and almost half of all AD patients have at least one ε4 allele. Recent studies suggest a bidirectional relationship exists between sleep and AD pathology. Sleep may play an important role in Aβ clearance, and getting good quality sleep vs. poor quality sleep might reduce the AD risk associated with neuroinflammation and the ε4 allele. Taken together, these findings are particularly important given the sleep disruptions commonly associated with AD and the increased burden disrupted sleep poses for AD caregivers. The current review aims to: (1) identify individuals at high risk for dementia who may benefit most from sleep interventions; (2) explore the role poor sleep quality plays in exacerbating AD type dementia; (3) examine the science of sleep interventions to date; and (4) provide a road map in pursuit of comprehensive sleep interventions, specifically targeted to promote cognitive function and delay progression of dementia.
    Full-text · Article · Dec 2014 · Frontiers in Aging Neuroscience
    • "Apo E is an established risk factor associated with Alzheimer's disease, cerebrovascular and coronary heart disease13. Apo E genotyping is clinically useful in subjects who have a predisposition to these diseases. Storage and transportation of blood samples collected from field is a difficult task. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Dried blood spotted on to filter paper has been found suitable for a large number of studies. In tropical countries with varying temperature conditions the use of dried blood needs to be validated. We carried out this study to assess the use of blood spotted filter paper as a transport system to study genotyping of Apo E gene. Fifty five patients visiting Cardiothoracic Neuroscience Centre (CNC) OPD at the All India Institute of Medical Sciences (AIIMS), New Delhi, and referred for lipid investigations to Cardiac Biochemistry Laboratory were selected at random. Blood was spotted on to Whatman 3 MM filter paper, dried and stored at room temperature. Genomic DNA was extracted and genotyping was carried out at the end of 0, 3 and 12 months. The study was further validated using samples collected on to filter paper from four centres and stored for eight years at room temperature. The temperature and humidity conditions of the centre varied widely. Fifty five samples collected on to filter paper showed exact match of the genotyping when compared to fresh blood. In dried blood samples collected and stored for 1 yr at room temperature DNA extraction and apo E genotyping was done successfully. The present results showed the feasibility of using dried blood samples on filter paper for apo E genotyping in tropical temperature. The findings need to be validated on a large sample before being recommended for use.
    No preview · Article · Mar 2012 · The Indian Journal of Medical Research
  • Source
    • "The structural APOE gene is polymorphic with three common alleles, designated as ε2, ε3 and ε4 which encode for E2, E3 and E4 proteins, respectively. Although several APOE polymorphisms have been identified, the APOE ε4 allele has been the most consistently associated with CHD and LDL-C levels (Table 2) (Anoop et al., 2010; Chang et al., 2010; Eichner et al., 2002; Teslovich et al., 2010; Willer et al., 2008). "

    Full-text · Chapter · Feb 2012
Show more