scholarly journals Apolipoprotein E promoter genotypes are not associated with white matter hyperintensity development in high-altitude careers

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Richard R. Chapleau ◽  
CharLee A. Martin ◽  
Summer R. Hughes ◽  
James C. Baldwin ◽  
John Sladky ◽  
...  
Keyword(s):  
White Matter ◽  
Apolipoprotein E ◽  
High Altitude ◽  
White Matter Hyperintensities ◽  
White Matter Hyperintensity ◽  
Chain Reaction ◽  
Promoter Regions ◽  
Altitude Exposure ◽  
Apoe Protein ◽  
Polymerase Chain

Abstract Objective This study sought to determine if there is an association between variants in the apolipoprotein E (ApoE) promoter regions and development of white matter hyperintensities (WMH) in military subjects who have been exposed to high altitude. In an earlier study, we found that ApoE status did not correlate with WMH development, and here we hypothesized that regulation of APOE protein expression may be protective. Results Our cohort of 92 subjects encountered altitude exposures above 25,000 feet mean sea level through their occupations as pilots or altitude chamber technicians. Using Taqman-style polymerase chain reaction genotyping and t-tests and two-way analyses of variance we found no significant association between ApoE promoter genotypes and the presence, volume, or quantity of WMHs after high altitude exposure. Taken together, the observations that neither ApoE genotype status nor promoter status are associated with WMH properties, we believe that the mechanism of action for developing WMH does not derive from ApoE, nor would therapies for ApoE-mediated neurodegeneration likely benefit high altitude operators.

scholarly journals Clinical assessement of the 8 genes on chromosome 3 with also MGMT gene promoter regions methylaton status in patients with breast cancer luminal hystotype

2017 ◽  
Vol 16 (4) ◽  
pp. 38-45
Author(s):  
D. A. Ryabchikov ◽  
I. K. Vorotnikov ◽  
T. P. Kazubskaya ◽  
S. S. Lukina ◽  
E. A. Filippova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Polymerase Chain Reaction ◽  
Normal Tissue ◽  
Methylation Status ◽  
Chromosome 3 ◽  
Epigenetic Changes ◽  
Chain Reaction ◽  
Promoter Regions ◽  
Polymerase Chain

Background. Epigenetic changes of TSG are supposed as the most fine and active genes regulation mechanism in particular breast cancer (BC) genes pathway development. The most valuable results are awaited for methylation role of genes located on the short arm of chromosome 3 with also MGMT gene (10q26) in BC pathogenesis because of their ambiguous data for methylation status in tumors. Objective: to illustrate the specific methylation role of the RASSF1A, SEMA3B, RARß2, RHOA, GPX1, USP4, DAG1, NKIRAS1 and MGMT genes promoter regions in BC pathogenesis. Materials and methods. Sample set of 174 BC patients consists of tumor and surrounding histologically normal tissue that were collected and clinically characterized in the N.N. Blokhin National Medical Research Center of Oncology. Two substantive methods were used to evaluate DNA methylation status. To analyse RASSF1A, SEMA3B, RARß2 and MGMT genes methylation we used polymerase chain reaction specific for the methylated allele. Whereas for analyses RHOA, GPX1, USP4, DAG1, NKIRAS1 promoter regions genes methylation status was used methyl sensitive restriction analyses with 2 methyl sensitive endonuclaeses HpaII and HhaI with subsequent polymerase chain reaction. Results. A statistically significant high frequency of RASSF1A, SEMA3B, RARß2, and MGMT genes methylation in epithelial breast tumors compared with histologically normal tissue from the same patients was shown. Significant correlation of RARß2 and MGMT genes methylation frequency considering the different clinical and morphological characteristics of the malignant process was revealed. The statistically significant relationship between methylation of RASSF1A, RARß2 and MGMT genes and patient survival is shown for the first time. Conclusion. The findings of epigenetic changes in the luminal BC supplement the “molecular picture” of this cancer and contribute to an understanding of its pathogenesis. The revealed features of investigated genes methylation can find clinical application for the development of modern approaches to prognosis, prevention and choice of tactics for treatment of BC in females of the Moscow region.

Abstract TP181: Serum Eiocosapentaenoic Acids Is Protective Against White Matter Lesions

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Daiki Takano ◽  
Takashi Yamazaki ◽  
Tetsuya Maeda ◽  
Yuichi Satoh ◽  
Yasuko Ikeda ◽  
...  
Keyword(s):  
White Matter ◽  
Cognitive Decline ◽  
White Matter Hyperintensities ◽  
Small Vessel Disease ◽  
White Matter Lesions ◽  
White Matter Hyperintensity ◽  
Partial Regression Coefficient ◽  
The Relationship ◽  
Total Pufa ◽  
Periventricular Hyperintensity

[Introduction] White matter hyperintensities (WMH) are considered manifestation of arteriosclerotic small vessel disease and WMH burden increases risk of ischemic stroke and cognitive decline. There are only a few evidences concerning the relationship between polyunsaturated fatty acids (PUFA) and WMH. The present study was designed to elucidate the association between WMH and PUFA profile including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and arachidonic acid (AA) in patients with Alzheimer’s disease (AD). [Methods] The present study was based on 119 patients who were diagnosed as having a probable AD according to the NINCDS-ADRDA criteria. Their mean age was 78.3 years old. All subjects underwent neuropsychological evaluation including mini mental state exam (MMSE) and 1.5-Tesla MRI. Fasting blood samples were also collected for the PUFA measurements. We measured the ratio of serum EPA, DHA and AA concentration to the total PUFA concentration. The WMH were evaluated on T2-weight images and classified into periventricular hyperintensity (PVH) and deep white matter hyperintensity (DWMH). The severity of WMH was graded 5 categories. We investigated the relationship between WMH and PUFA profiles. [Results] The EPA ratio correlated negatively with both PVH (rs=-0.2036, p=0.0264) and DWMH grade (rs=-0.3155, p=0.0005). It remained still significant after adjustment for age, sex, statins use, antithrombotics use, mean blood pressure and presence of hypertension (standardized partial regression coefficient(β)=-0.2516, p=0.0122 for PVH, β=-0.3598, p=0.0001 for DWMH). Neither DHA nor AA ratio correlated with DWMH or PVH grade. The EPA ratio but not DHA or AA ratio correlated positively with total MMSE score (rs=0.2310, p=0.0115). [Conclusions] Our data revealed that the serum EPA was protective against WMH as well as cognitive decline in AD patients. Pathophysiology underlying WMH is complex and the possible mechanisms involved in the pathogenesis of WMH encompass incomplete brain ischemia, increased permeability of blood-brain barrier, and inflammation responses. The relationship between serum EPA and WMH can be partly explained by those anti-ischemic and anti-arteriosclerotic effects of EPA.

scholarly journals White matter hyperintensities are common in midlife and already associated with cognitive decline

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Tracy d’Arbeloff ◽  
Maxwell L Elliott ◽  
Annchen R Knodt ◽  
Tracy R Melzer ◽  
Ross Keenan ◽  
...  
Keyword(s):  
White Matter ◽  
Cognitive Decline ◽  
White Matter Hyperintensities ◽  
Clinical Symptoms ◽  
White Matter Hyperintensity ◽  
Dementia Prevention ◽  
Increased Risk ◽  
Weighted Magnetic Resonance Imaging ◽  
Intervention Trials ◽  
The Brain

Abstract White matter hyperintensities proliferate as the brain ages and are associated with increased risk for cognitive decline as well as Alzheimer’s disease and related dementias. As such, white matter hyperintensities have been targeted as a surrogate biomarker in intervention trials with older adults. However, it is unclear at what stage of aging white matter hyperintensities begin to relate to cognition and if they may be a viable target for early prevention. In the Dunedin Study, a population-representative cohort followed since birth, we measured white matter hyperintensities in 843 45-year-old participants using T2-weighted magnetic resonance imaging and we assessed cognitive decline from childhood to midlife. We found that white matter hyperintensities were common at age 45 and that white matter hyperintensity volume was modestly associated with both lower childhood (ß = −0.08, P = 0.013) and adult IQ (ß=−0.15, P < 0.001). Moreover, white matter hyperintensity volume was associated with greater cognitive decline from childhood to midlife (ß=−0.09, P < 0.001). Our results demonstrate that a link between white matter hyperintensities and early signs of cognitive decline is detectable decades before clinical symptoms of dementia emerge. Thus, white matter hyperintensities may be a useful surrogate biomarker for identifying individuals in midlife at risk for future accelerated cognitive decline and selecting participants for dementia prevention trials.

scholarly journals Brain amyloid and vascular risk are related to distinct white matter hyperintensity patterns

2020 ◽  
pp. 0271678X2095760
Author(s):  
Lene Pålhaugen ◽  
Carole H Sudre ◽  
Sandra Tecelao ◽  
Arne Nakling ◽  
Ina S Almdahl ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
White Matter ◽  
White Matter Hyperintensities ◽  
Framingham Risk Score ◽  
Early Stage ◽  
White Matter Hyperintensity ◽  
Group Differences ◽  
Vascular Risk ◽  
Automated Algorithm ◽  
Framingham Risk

White matter hyperintensities (WMHs) are associated with vascular risk and Alzheimer’s disease. In this study, we examined relations between WMH load and distribution, amyloid pathology and vascular risk in 339 controls and cases with either subjective (SCD) or mild cognitive impairment (MCI). Regional deep (DWMH) and periventricular (PWMH) WMH loads were determined using an automated algorithm. We stratified on Aβ1-42 pathology (Aβ+/−) and analyzed group differences, as well as associations with Framingham Risk Score for cardiovascular disease (FRS-CVD) and age. Occipital PWMH ( p = 0.001) and occipital DWMH ( p = 0.003) loads were increased in SCD-Aβ+ compared with Aβ− controls. In MCI-Aβ+ compared with Aβ− controls, there were differences in global WMH ( p = 0.003), as well as occipital DWMH ( p = 0.001) and temporal DWMH ( p = 0.002) loads. FRS-CVD was associated with frontal PWMHs ( p = 0.003) and frontal DWMHs ( p = 0.005), after adjusting for age. There were associations between global and all regional WMH loads and age. In summary, posterior WMH loads were increased in SCD-Aβ+ and MCI-Aβ+ cases, whereas frontal WMHs were associated with vascular risk. The differences in WMH topography support the use of regional WMH load as an early-stage marker of etiology.

Apolipoprotein E polymorphism determined by restriction enzyme analysis of DNA amplified by polymerase chain reaction: convenient alternative to phenotyping by isoelectric focusing

1990 ◽  
Vol 36 (12) ◽  
pp. 2087-2092 ◽  
Author(s):  
K Kontula ◽  
K Aalto-Setälä ◽  
T Kuusi ◽  
L Hämäläinen ◽  
A C Syvänen
Keyword(s):  
Polymerase Chain Reaction ◽  
Genetic Variation ◽  
Apolipoprotein E ◽  
Isoelectric Focusing ◽  
Restriction Enzyme ◽  
Enzyme Analysis ◽  
Variant Form ◽  
Chain Reaction ◽  
Apo E ◽  
Polymerase Chain

Abstract Three common alleles determine six apolipoprotein E (apo E) phenotypes that are associated with variations in serum cholesterol in the population. This genetic variation results from single nucleotide alterations at two DNA loci encoding the amino acid residues 112 and 158 of apo E. We compared results of apo E phenotyping carried out by isoelectric focusing with those of apo E genotyping accomplished by direct DNA analysis. In the latter, the target DNA was amplified by the polymerase chain reaction (PCR) and subsequently analyzed by digestion with the restriction enzyme Hha I, followed by polyacrylamide gel electrophoresis of the cleavage products. With one exception, these two techniques yielded similar results from all 40 samples tested. In addition, a rare variant form of apo E (phenotype E1) was analyzed separately and incorrectly diagnosed as E2 by the Hha I digestion method; the anticipated mutation in the codon 127 was, however, confirmed by demonstration of a new Taq I restriction site in this variant gene. These data confirm that the common isoforms of apo E usually arise from genetic variation of the codons 112 and 158 and demonstrate the feasibility of the PCR technique in apo E genotyping.

scholarly journals Quantification of apolipoprotein E receptors in human brain-derived cell lines by real-time polymerase chain reaction

2005 ◽  
Vol 26 (6) ◽  
pp. 813-823 ◽  
Author(s):  
Shanaka Thilakawardhana ◽  
David M. Everett ◽  
Paul R. Murdock ◽  
Colin Dingwall ◽  
James S. Owen
Keyword(s):  
Polymerase Chain Reaction ◽  
Human Brain ◽  
Apolipoprotein E ◽  
Real Time ◽  
Cell Lines ◽  
Chain Reaction ◽  
Polymerase Chain

Development of a new biochip array for APOE4 classification from plasma samples using immunoassay-based methods

2018 ◽  
Vol 56 (5) ◽  
pp. 796-802 ◽  
Author(s):  
Sigrun Badrnya ◽  
Tara Doherty ◽  
Ciaran Richardson ◽  
Robert I. McConnell ◽  
John V. Lamont ◽  
...  
Keyword(s):  
Specific Information ◽  
Degenerative Diseases ◽  
Chain Reaction ◽  
Array Technology ◽  
Apoe Protein ◽  
Additional Protein ◽  
Polymerase Chain ◽  
Simultaneous Immunoassay ◽  
Risk Prognosis ◽  
Disease Stages

AbstractBackground:Apolipoprotein E (APOE) is a key player in lipid transport and metabolism and exists in three common isoforms: APOE2, APOE3 and APOE4. The presence of theE4allelic variant is recognized as a major genetic risk factor for dementia and other chronic (neuro)degenerative diseases. The availability of a validated assay for rapid and reliable APOE4 classification is therefore advantageous.Methods:Biochip array technology (BAT) was successfully applied to identify directly the APOE4 status from plasma within 3 h, through simultaneous immunoassay-based detection of both specific APOE4 and total APOE levels.Results:Samples (n=432) were first genotyped by polymerase chain reaction (PCR), and thereafter, using BAT, the corresponding plasma was identified as null, heterozygous or homozygous for theE4allele by calculating the ratio of APOE4 to total APOE protein. Two centers based in Austria and Ireland correctly classified 170 and 262 samples, respectively, and achieved 100% sensitivity and specificity.Conclusions:This chemiluminescent biochip-based sandwich immunoarray provides a novel platform to detect rapidly and accurately an individual’sAPOE4status directly from plasma. TheE4genotype of individuals has been shown previously to affect presymptomatic risk, prognosis and treatment response for a variety of diseases, including Alzheimer’s disease. The biochip’s potential for being incorporated in quantitative protein biomarker arrays capable of analyzing disease stages makes it a superior alternative to PCR-basedAPOEgenotyping and may deliver additional protein-specific information on a variety of diseases in the future.

White matter hyperintensities on MRI in high-altitude U-2 pilots

Neurology ◽  
2014 ◽  
Vol 82 (12) ◽  
pp. 1102-1103 ◽  
Author(s):  
J. Hellmann-Regen ◽  
K. Hinkelmann ◽  
F. Regen ◽  
S. A. McGuire ◽  
S. Antonio
Keyword(s):  
White Matter ◽  
High Altitude ◽  
White Matter Hyperintensities
Sign in / Sign up

Export Citation Format

Share Document