Genetic studies in rheumatoid arthritis : familial studies and analysis of relationships to atherothrombotic comorbidity
Background. Rheumatoid arthritis (RA) is an autoimmune disease mainly affecting the joints but has also extra articular manifestations and an increased cardiovascular (CV) co-morbidity. Rheumatoid factor (RF) and antibodies against citrullinated proteins/peptides (ACPA) are diagnostically important...
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ftumeauniv:oai:DiVA.org:umu-52956 2023-10-09T21:54:36+02:00 Genetic studies in rheumatoid arthritis : familial studies and analysis of relationships to atherothrombotic comorbidity Ärlestig, Lisbeth 2012 application/pdf http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-52956 eng eng Reumatologi Umeå : Umeå Universitet Umeå University medical dissertations, 0346-6612 1484 http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-52956 urn:isbn:978-91-7459-383-9 info:eu-repo/semantics/openAccess Rheumatoid arthritis genetics familial studies ACPA and cardiovascular co-morbidity Rheumatology and Autoimmunity Reumatologi och inflammation Doctoral thesis, comprehensive summary info:eu-repo/semantics/doctoralThesis text 2012 ftumeauniv 2023-09-22T13:49:33Z Background. Rheumatoid arthritis (RA) is an autoimmune disease mainly affecting the joints but has also extra articular manifestations and an increased cardiovascular (CV) co-morbidity. Rheumatoid factor (RF) and antibodies against citrullinated proteins/peptides (ACPA) are diagnostically important and are related to a more severe disease. The aetiology is unknown but RA is considered a complex disease caused by both genetic and environmental factors. The heritability is estimated to be 60% with the main contribution from the HLA region. The relative homogeneity of the population in northern Sweden due to low immigration and founder effects has shown to be suitable for genetic studies. Objectives. The aim of this thesis has been to identify genes contributing to the susceptibility of RA and the CV co-morbidity in particular. To achieve this, multi-case families from the four northern most counties of Sweden were collected for linkage studies to identify susceptibility genes. Association studies with genetic polymorphisms in genes, involved in inflammation or being of importance for atherothrombotic manifestations (ATM) in the general population, were performed in RA-patients concerning ATM e.g. myocardial infarction, angina pectoris with intervention, stroke/TIA, deep vein thrombosis/pulmonary embolism (DVT/PE) at follow-up. Methods & Results. 47 families with 134 affected and 216 unaffected relatives were included in a genome-wide linkage study (GWL) performed with microsatellite markers at an average of 10cM resolution analysed using ABI PRISM 3730 DNA sequencer and non-parametric multipoint linkage in the Merlin program. Eight linked loci were identified with HLA as the most significant and a novel region on chromosome 14. In a follow-up analysis on a custom Illumina chip, with 13 additional families, yielding a total of 198 affected and 197 unaffected relatives. The majority of the 1536 single nucleotide polymorphisms (SNPs) used in the Illumina follow-up analyses was focused on chromosome 14. ... Doctoral or Postdoctoral Thesis Northern Sweden Umeå University: Publications (DiVA) |
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Open Polar |
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Umeå University: Publications (DiVA) |
op_collection_id |
ftumeauniv |
language |
English |
topic |
Rheumatoid arthritis genetics familial studies ACPA and cardiovascular co-morbidity Rheumatology and Autoimmunity Reumatologi och inflammation |
spellingShingle |
Rheumatoid arthritis genetics familial studies ACPA and cardiovascular co-morbidity Rheumatology and Autoimmunity Reumatologi och inflammation Ärlestig, Lisbeth Genetic studies in rheumatoid arthritis : familial studies and analysis of relationships to atherothrombotic comorbidity |
topic_facet |
Rheumatoid arthritis genetics familial studies ACPA and cardiovascular co-morbidity Rheumatology and Autoimmunity Reumatologi och inflammation |
description |
Background. Rheumatoid arthritis (RA) is an autoimmune disease mainly affecting the joints but has also extra articular manifestations and an increased cardiovascular (CV) co-morbidity. Rheumatoid factor (RF) and antibodies against citrullinated proteins/peptides (ACPA) are diagnostically important and are related to a more severe disease. The aetiology is unknown but RA is considered a complex disease caused by both genetic and environmental factors. The heritability is estimated to be 60% with the main contribution from the HLA region. The relative homogeneity of the population in northern Sweden due to low immigration and founder effects has shown to be suitable for genetic studies. Objectives. The aim of this thesis has been to identify genes contributing to the susceptibility of RA and the CV co-morbidity in particular. To achieve this, multi-case families from the four northern most counties of Sweden were collected for linkage studies to identify susceptibility genes. Association studies with genetic polymorphisms in genes, involved in inflammation or being of importance for atherothrombotic manifestations (ATM) in the general population, were performed in RA-patients concerning ATM e.g. myocardial infarction, angina pectoris with intervention, stroke/TIA, deep vein thrombosis/pulmonary embolism (DVT/PE) at follow-up. Methods & Results. 47 families with 134 affected and 216 unaffected relatives were included in a genome-wide linkage study (GWL) performed with microsatellite markers at an average of 10cM resolution analysed using ABI PRISM 3730 DNA sequencer and non-parametric multipoint linkage in the Merlin program. Eight linked loci were identified with HLA as the most significant and a novel region on chromosome 14. In a follow-up analysis on a custom Illumina chip, with 13 additional families, yielding a total of 198 affected and 197 unaffected relatives. The majority of the 1536 single nucleotide polymorphisms (SNPs) used in the Illumina follow-up analyses was focused on chromosome 14. ... |
format |
Doctoral or Postdoctoral Thesis |
author |
Ärlestig, Lisbeth |
author_facet |
Ärlestig, Lisbeth |
author_sort |
Ärlestig, Lisbeth |
title |
Genetic studies in rheumatoid arthritis : familial studies and analysis of relationships to atherothrombotic comorbidity |
title_short |
Genetic studies in rheumatoid arthritis : familial studies and analysis of relationships to atherothrombotic comorbidity |
title_full |
Genetic studies in rheumatoid arthritis : familial studies and analysis of relationships to atherothrombotic comorbidity |
title_fullStr |
Genetic studies in rheumatoid arthritis : familial studies and analysis of relationships to atherothrombotic comorbidity |
title_full_unstemmed |
Genetic studies in rheumatoid arthritis : familial studies and analysis of relationships to atherothrombotic comorbidity |
title_sort |
genetic studies in rheumatoid arthritis : familial studies and analysis of relationships to atherothrombotic comorbidity |
publisher |
Reumatologi |
publishDate |
2012 |
url |
http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-52956 |
genre |
Northern Sweden |
genre_facet |
Northern Sweden |
op_relation |
Umeå University medical dissertations, 0346-6612 1484 http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-52956 urn:isbn:978-91-7459-383-9 |
op_rights |
info:eu-repo/semantics/openAccess |
_version_ |
1779318245713510400 |