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Common FXIII and Fibrinogen Polymorphisms in Abdominal Aortic Aneurysms

INTRODUCTION: Abdominal aortic aneurysms (AAA) are characterized by a progressive dilatation of the abdominal aorta, and are associated with a high risk of rupture once the dilatation exceeds 55 mm in diameter. A large proportion of AAA develops an intraluminal thrombus, which contributes to hypoxia...

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Autores principales: Macrae, Fraser L., Lee Evans, Hannah, Bridge, Katherine I., Johnson, Anne, Scott, D. Julian A., Ariëns, Robert A. S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4226572/
https://www.ncbi.nlm.nih.gov/pubmed/25384012
http://dx.doi.org/10.1371/journal.pone.0112407
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author Macrae, Fraser L.
Lee Evans, Hannah
Bridge, Katherine I.
Johnson, Anne
Scott, D. Julian A.
Ariëns, Robert A. S.
author_facet Macrae, Fraser L.
Lee Evans, Hannah
Bridge, Katherine I.
Johnson, Anne
Scott, D. Julian A.
Ariëns, Robert A. S.
author_sort Macrae, Fraser L.
collection PubMed
description INTRODUCTION: Abdominal aortic aneurysms (AAA) are characterized by a progressive dilatation of the abdominal aorta, and are associated with a high risk of rupture once the dilatation exceeds 55 mm in diameter. A large proportion of AAA develops an intraluminal thrombus, which contributes to hypoxia, inflammation and tissue degradation. We have previously shown that patients with AAA produce clots with altered structure which is more resistant to fibrinolysis. The aim of this study was to investigate genetic polymorphisms of FXIII and fibrinogen in AAA to identify how changes to these proteins may play a role in the development of AAA. METHODS: Subjects of Western/European descent, ≥55 years of age (520 AAA patients and 449 controls) were genotyped for five polymorphisms (FXIII-A Val34Leu, FXIII-B His95Arg, FXIII-B Splice Variant (intron K nt29576C-G), Fib-A Thr312Ala and Fib-B Arg448Lys) by RT-PCR. Data were analysed by χ2 test and CubeX. RESULTS: The FXIII-B Arg95 allele associated with AAA (Relative risk - 1.240, CI 1.093–1.407, P = 0.006). There was no association between FXIII-A Val34Leu, FXIII-B Splice Variant, Fib-A Thr312Ala or Fib-B Arg448Lys and AAA. FXIII-B His95Arg and FXIII-B Splice variant (intron K nt29576C-G) were in negative linkage disequilibrium (D’ = −0.609, p = 0.011). DISCUSSION: The FXIII-B Arg95 variant is associated with an increased risk of AAA. These data suggest a possible role for FXIII in AAA pathogenesis.
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spelling pubmed-42265722014-11-13 Common FXIII and Fibrinogen Polymorphisms in Abdominal Aortic Aneurysms Macrae, Fraser L. Lee Evans, Hannah Bridge, Katherine I. Johnson, Anne Scott, D. Julian A. Ariëns, Robert A. S. PLoS One Research Article INTRODUCTION: Abdominal aortic aneurysms (AAA) are characterized by a progressive dilatation of the abdominal aorta, and are associated with a high risk of rupture once the dilatation exceeds 55 mm in diameter. A large proportion of AAA develops an intraluminal thrombus, which contributes to hypoxia, inflammation and tissue degradation. We have previously shown that patients with AAA produce clots with altered structure which is more resistant to fibrinolysis. The aim of this study was to investigate genetic polymorphisms of FXIII and fibrinogen in AAA to identify how changes to these proteins may play a role in the development of AAA. METHODS: Subjects of Western/European descent, ≥55 years of age (520 AAA patients and 449 controls) were genotyped for five polymorphisms (FXIII-A Val34Leu, FXIII-B His95Arg, FXIII-B Splice Variant (intron K nt29576C-G), Fib-A Thr312Ala and Fib-B Arg448Lys) by RT-PCR. Data were analysed by χ2 test and CubeX. RESULTS: The FXIII-B Arg95 allele associated with AAA (Relative risk - 1.240, CI 1.093–1.407, P = 0.006). There was no association between FXIII-A Val34Leu, FXIII-B Splice Variant, Fib-A Thr312Ala or Fib-B Arg448Lys and AAA. FXIII-B His95Arg and FXIII-B Splice variant (intron K nt29576C-G) were in negative linkage disequilibrium (D’ = −0.609, p = 0.011). DISCUSSION: The FXIII-B Arg95 variant is associated with an increased risk of AAA. These data suggest a possible role for FXIII in AAA pathogenesis. Public Library of Science 2014-11-10 /pmc/articles/PMC4226572/ /pubmed/25384012 http://dx.doi.org/10.1371/journal.pone.0112407 Text en © 2014 Macrae et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Macrae, Fraser L.
Lee Evans, Hannah
Bridge, Katherine I.
Johnson, Anne
Scott, D. Julian A.
Ariëns, Robert A. S.
Common FXIII and Fibrinogen Polymorphisms in Abdominal Aortic Aneurysms
title Common FXIII and Fibrinogen Polymorphisms in Abdominal Aortic Aneurysms
title_full Common FXIII and Fibrinogen Polymorphisms in Abdominal Aortic Aneurysms
title_fullStr Common FXIII and Fibrinogen Polymorphisms in Abdominal Aortic Aneurysms
title_full_unstemmed Common FXIII and Fibrinogen Polymorphisms in Abdominal Aortic Aneurysms
title_short Common FXIII and Fibrinogen Polymorphisms in Abdominal Aortic Aneurysms
title_sort common fxiii and fibrinogen polymorphisms in abdominal aortic aneurysms
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4226572/
https://www.ncbi.nlm.nih.gov/pubmed/25384012
http://dx.doi.org/10.1371/journal.pone.0112407
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