Once again a thesis does more for clarifying stroke than all the stroke associations put together. Read the riot act to your doctor until a stroke protocol is created from this.
A study of epigenetics in ischaemic stroke
Author:
Pogoryelova, Oksana
Awarding Body:
University of Aberdeen
Current Institution:
University of Aberdeen
Date of Award:
2013
Availability of Full Text:
EThOS Persistent ID:
uk.bl.ethos.582717
Supervisor:
Not available
Sponsor:
Not available
Qualification Name:
Thesis (Ph.D.)
Qualification Level:
Doctoral
Abstract:
Author: Pogoryelova, Oksana| Access through EThOS: | |
| Access through Institution: |
Ischaemic stroke rates are expected to rise significantly in the
next decades due to an aging population. This increases the demand for
new stroke biomarkers for early detection of patients at risk and new
targets for treatment. It has been hypothesized that epigenetics may be
important in the aetiology of stroke. The study consisted of three types
of investigation: analysis of candidate gene polymorphism, candidate
gene methylation analysis and epigenome-wide methylation analysis (EWAS)
of pooled stroke and control samples. The stroke types studied were
large vessel disease (LVD), small vessel disease (SVD) and cardioembolic
stroke (CE). DNA from peripheral blood samples was used for EWAS and
methylation analysis. Significant increases in rare allele frequency
were observed in the EHMT2 and DNMT3B genes for all stroke cases; MBD2,
DNMT3B and DNMT3L polymorphisms were associated with LVD. IL10, SOD3,
LINE1 and PITX2 were significantly hypomethylated in LVD. IL10 and
ALOX15 were hypomethylated in CE compared to controls. Methylation
levels of following genes were associated with age (LINE1, IL10, MTHFR,
TNFα, and PITX2), gender (SOD3 and LINE1), total cholesterol level
(SOD3) and systolic blood pressure (IL10). HDAC9 genetic polymorphism
was associated with the MTHFR methylation level. A distinctive
methylation pattern for each stroke subtype was found by EWAS. The CE
pool was hypomethylated at genome, chromosome and gene level, while LVD
and SVD pools had regions with higher and lower methylation levels
compared to the controls. GNAS was identified as new candidate gene by
EWAS. The results suggested that genetic polymorphism and DNA
methylation levels of candidate genes were associated with ischaemic
stroke. Stroke subtypes had distinct methylation profiles suggesting
differences in underlying aetiology. Variations in methylation levels
detected in this study could lead to identification of specific
biomarkers. Replication on a large number of subjects is required before
final conclusions can be drawn.
- See more at: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.582717#sthash.rU4z1697.dpufAwarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2013 Availability of Full Text:
Access through EThOS:
Thesis available to order.
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Access through Institution:
http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?application=DIGITOOL-3&owner=resourcediscovery&custom_att_2=simple_viewer&pid=201969
EThOS Persistent ID: uk.bl.ethos.582717 Supervisor: Not available Sponsor: Not available Qualification Name: Thesis (Ph.D.) Qualification Level:
Doctoral Abstract:
Ischaemic stroke rates are expected to rise significantly in the next decades due to an aging population. This increases the demand for new stroke biomarkers for early detection of patients at risk and new targets for treatment. It has been hypothesized that epigenetics may be important in the aetiology of stroke.
Author:
Pogoryelova, Oksana
Awarding Body:
University of Aberdeen
Current Institution:
University of Aberdeen
Date of Award:
2013
Availability of Full Text:
EThOS Persistent ID:
uk.bl.ethos.582717
Supervisor:
Not available
Sponsor:
Not available
Qualification Name:
Thesis (Ph.D.)
Qualification Level:
Doctoral
Abstract:
| Access through EThOS: | |
| Access through Institution: |
Ischaemic stroke rates are expected to rise significantly in the
next decades due to an aging population. This increases the demand for
new stroke biomarkers for early detection of patients at risk and new
targets for treatment. It has been hypothesized that epigenetics may be
important in the aetiology of stroke. The study consisted of three types
of investigation: analysis of candidate gene polymorphism, candidate
gene methylation analysis and epigenome-wide methylation analysis (EWAS)
of pooled stroke and control samples. The stroke types studied were
large vessel disease (LVD), small vessel disease (SVD) and cardioembolic
stroke (CE). DNA from peripheral blood samples was used for EWAS and
methylation analysis. Significant increases in rare allele frequency
were observed in the EHMT2 and DNMT3B genes for all stroke cases; MBD2,
DNMT3B and DNMT3L polymorphisms were associated with LVD. IL10, SOD3,
LINE1 and PITX2 were significantly hypomethylated in LVD. IL10 and
ALOX15 were hypomethylated in CE compared to controls. Methylation
levels of following genes were associated with age (LINE1, IL10, MTHFR,
TNFα, and PITX2), gender (SOD3 and LINE1), total cholesterol level
(SOD3) and systolic blood pressure (IL10). HDAC9 genetic polymorphism
was associated with the MTHFR methylation level. A distinctive
methylation pattern for each stroke subtype was found by EWAS. The CE
pool was hypomethylated at genome, chromosome and gene level, while LVD
and SVD pools had regions with higher and lower methylation levels
compared to the controls. GNAS was identified as new candidate gene by
EWAS. The results suggested that genetic polymorphism and DNA
methylation levels of candidate genes were associated with ischaemic
stroke. Stroke subtypes had distinct methylation profiles suggesting
differences in underlying aetiology. Variations in methylation levels
detected in this study could lead to identification of specific
biomarkers. Replication on a large number of subjects is required before
final conclusions can be drawn.
- See more at: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.582717#sthash.rU4z1697.dpuf
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