Common FXIII and fibrinogen polymorphisms in abdominal aortic aneurysms.
BACKGROUND
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).


CONCLUSIONS
The FXIII-B Arg95 variant is associated with an increased risk of AAA. These data suggest a possible role for FXIII in AAA pathogenesis.
Theme Thrombosis, Division of Cardiovascular and Diabetes Research, Leeds institute for Cardiovascular and Metabolic Medicine, Multidisciplinary Cardiovascular Research Centre, University of Leeds, Leeds, United Kingdom.
Fraser L
FL
Macrae
Theme Thrombosis, Division of Cardiovascular and Diabetes Research, Leeds institute for Cardiovascular and Metabolic Medicine, Multidisciplinary Cardiovascular Research Centre, University of Leeds, Leeds, United Kingdom.
Hannah Lee
HL
Evans
Theme Thrombosis, Division of Cardiovascular and Diabetes Research, Leeds institute for Cardiovascular and Metabolic Medicine, Multidisciplinary Cardiovascular Research Centre, University of Leeds, Leeds, United Kingdom; Leeds Vascular Institute, The General Infirmary at Leeds, Leeds, United Kingdom.
Katherine I
KI
Bridge
Theme Thrombosis, Division of Cardiovascular and Diabetes Research, Leeds institute for Cardiovascular and Metabolic Medicine, Multidisciplinary Cardiovascular Research Centre, University of Leeds, Leeds, United Kingdom; Leeds Vascular Institute, The General Infirmary at Leeds, Leeds, United Kingdom.
Anne
A
Johnson
Theme Thrombosis, Division of Cardiovascular and Diabetes Research, Leeds institute for Cardiovascular and Metabolic Medicine, Multidisciplinary Cardiovascular Research Centre, University of Leeds, Leeds, United Kingdom; Leeds Vascular Institute, The General Infirmary at Leeds, Leeds, United Kingdom.
D Julian A
DJ
Scott
Theme Thrombosis, Division of Cardiovascular and Diabetes Research, Leeds institute for Cardiovascular and Metabolic Medicine, Multidisciplinary Cardiovascular Research Centre, University of Leeds, Leeds, United Kingdom.
Robert A S
RA
Ariëns
D000368:Aged; D000369:Aged, 80 and over; D017544:Aortic Aneurysm, Abdominal / Q000235:genetics* / Q000473:pathology; D001120:Arginine / Q000235:genetics; D026122:Factor XIIIa / Q000235:genetics*; D005340:Fibrinogen / Q000235:genetics*; D056726:Genetic Association Studies; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics*
D005340:Fibrinogen; D001120:Arginine; D026122:Factor XIIIa