Genetic aspects of stroke : association and linkage studies in a northern Swedish population
Stroke is a common, multifactorial cardiovascular disease. A stroke event is the result of traditional risk factors (i.e. hypertension, diabetes, smoking), environmental exposures and genetic factors in a complex interplay. The genetic contribution is, as estimated by studies on the influence of fam...
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Umeå universitet, Institutionen för folkhälsa och klinisk medicin
2005
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ftumeauniv:oai:DiVA.org:umu-668 2023-10-09T21:54:38+02:00 Genetic aspects of stroke : association and linkage studies in a northern Swedish population Wiklund, Per-Gunnar 2005 application/pdf http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-668 eng eng Umeå universitet, Institutionen för folkhälsa och klinisk medicin Umeå : Folkhälsa och klinisk medicin Umeå University medical dissertations, 0346-6612 999 http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-668 urn:isbn:91-7305-999-4 info:eu-repo/semantics/openAccess Internal medicine stroke genetics polymorphism association linkage risk factors plasminogen activator inhibitor-1 tissue plasminogen activator angiotensin converting enzyme angiotensin II receptor type 1 phosphodiesterase 4D Invärtesmedicin Clinical Medicine Klinisk medicin Doctoral thesis, comprehensive summary info:eu-repo/semantics/doctoralThesis text 2005 ftumeauniv 2023-09-22T13:52:11Z Stroke is a common, multifactorial cardiovascular disease. A stroke event is the result of traditional risk factors (i.e. hypertension, diabetes, smoking), environmental exposures and genetic factors in a complex interplay. The genetic contribution is, as estimated by studies on the influence of family history on the risk of stroke, limited on the individual level, and overridden by, for example the excess risk associated with smoking. On the population level, and as a means to better understand the etiology of stroke, genetics can play a major role. Northern Sweden is well suited for studying the genetic aspects of stroke. The population shows signs of founder effects, and is relatively homogeneous. Large-scale cardiovascular health surveys, the MONICA Project and the Västerbotten Intervention Program, allow studies on risk factors in relation to stroke. Two prospective nested case-referent study samples, (113 cases and 226 controls; 275 cases and 549 controls), and a set of 56 families (117 affected) were collected for functional candidate gene association, and linkage, studies. The selected candidate genes included haemostatic factors and genes within the renin angiotensin system (RAS). Functional single nucleotide polymorphisms (SNPs) that influence the levels of PAI-1 (PAI-1 4G/5G), and tPA (tPA -7,351C>T), have been identified. The angiotensin converting enzyme insertion/deletion polymorphism (ACE I/D) has been shown to be associated with ischaemic stroke. The angiotensin II receptor type 1 A1166C polymorphism (AT1R A1166C), less extensively studied, has been suggested to be associated with stroke, and to interact with the ACE I/D. We found that the PAI-1 4G/4G genotype was associated with an increased risk of future ischaemic stroke (OR 1.79, 95%CI 1.01-3.19), and this was replicated in a second study sample. Furthermore, levels of serum triglycerides modulated the effect of the genotype. In the study on tPA, no association between the tPA -7,351C>T polymorphism and the risk of stroke was found in ... Doctoral or Postdoctoral Thesis Northern Sweden Umeå University: Publications (DiVA) |
institution |
Open Polar |
collection |
Umeå University: Publications (DiVA) |
op_collection_id |
ftumeauniv |
language |
English |
topic |
Internal medicine stroke genetics polymorphism association linkage risk factors plasminogen activator inhibitor-1 tissue plasminogen activator angiotensin converting enzyme angiotensin II receptor type 1 phosphodiesterase 4D Invärtesmedicin Clinical Medicine Klinisk medicin |
spellingShingle |
Internal medicine stroke genetics polymorphism association linkage risk factors plasminogen activator inhibitor-1 tissue plasminogen activator angiotensin converting enzyme angiotensin II receptor type 1 phosphodiesterase 4D Invärtesmedicin Clinical Medicine Klinisk medicin Wiklund, Per-Gunnar Genetic aspects of stroke : association and linkage studies in a northern Swedish population |
topic_facet |
Internal medicine stroke genetics polymorphism association linkage risk factors plasminogen activator inhibitor-1 tissue plasminogen activator angiotensin converting enzyme angiotensin II receptor type 1 phosphodiesterase 4D Invärtesmedicin Clinical Medicine Klinisk medicin |
description |
Stroke is a common, multifactorial cardiovascular disease. A stroke event is the result of traditional risk factors (i.e. hypertension, diabetes, smoking), environmental exposures and genetic factors in a complex interplay. The genetic contribution is, as estimated by studies on the influence of family history on the risk of stroke, limited on the individual level, and overridden by, for example the excess risk associated with smoking. On the population level, and as a means to better understand the etiology of stroke, genetics can play a major role. Northern Sweden is well suited for studying the genetic aspects of stroke. The population shows signs of founder effects, and is relatively homogeneous. Large-scale cardiovascular health surveys, the MONICA Project and the Västerbotten Intervention Program, allow studies on risk factors in relation to stroke. Two prospective nested case-referent study samples, (113 cases and 226 controls; 275 cases and 549 controls), and a set of 56 families (117 affected) were collected for functional candidate gene association, and linkage, studies. The selected candidate genes included haemostatic factors and genes within the renin angiotensin system (RAS). Functional single nucleotide polymorphisms (SNPs) that influence the levels of PAI-1 (PAI-1 4G/5G), and tPA (tPA -7,351C>T), have been identified. The angiotensin converting enzyme insertion/deletion polymorphism (ACE I/D) has been shown to be associated with ischaemic stroke. The angiotensin II receptor type 1 A1166C polymorphism (AT1R A1166C), less extensively studied, has been suggested to be associated with stroke, and to interact with the ACE I/D. We found that the PAI-1 4G/4G genotype was associated with an increased risk of future ischaemic stroke (OR 1.79, 95%CI 1.01-3.19), and this was replicated in a second study sample. Furthermore, levels of serum triglycerides modulated the effect of the genotype. In the study on tPA, no association between the tPA -7,351C>T polymorphism and the risk of stroke was found in ... |
format |
Doctoral or Postdoctoral Thesis |
author |
Wiklund, Per-Gunnar |
author_facet |
Wiklund, Per-Gunnar |
author_sort |
Wiklund, Per-Gunnar |
title |
Genetic aspects of stroke : association and linkage studies in a northern Swedish population |
title_short |
Genetic aspects of stroke : association and linkage studies in a northern Swedish population |
title_full |
Genetic aspects of stroke : association and linkage studies in a northern Swedish population |
title_fullStr |
Genetic aspects of stroke : association and linkage studies in a northern Swedish population |
title_full_unstemmed |
Genetic aspects of stroke : association and linkage studies in a northern Swedish population |
title_sort |
genetic aspects of stroke : association and linkage studies in a northern swedish population |
publisher |
Umeå universitet, Institutionen för folkhälsa och klinisk medicin |
publishDate |
2005 |
url |
http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-668 |
genre |
Northern Sweden |
genre_facet |
Northern Sweden |
op_relation |
Umeå University medical dissertations, 0346-6612 999 http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-668 urn:isbn:91-7305-999-4 |
op_rights |
info:eu-repo/semantics/openAccess |
_version_ |
1779318304470466560 |