RT Journal Article
SR Electronic
T1 Fibrinogen Aα Thr312Ala polymorphism is associated with chronic thromboembolic pulmonary hypertension
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 736
OP 741
DO 10.1183/09031936.00055107
VO 31
IS 4
A1 J. Suntharalingam
A1 K. Goldsmith
A1 V. van Marion
A1 L. Long
A1 C. M. Treacy
A1 F. Dudbridge
A1 M. R. Toshner
A1 J. Pepke-Zaba
A1 J. C. J. Eikenboom
A1 N. W. Morrell
YR 2008
UL http://erj.ersjournals.com/content/31/4/736.abstract
AB Although chronic thromboembolic pulmonary hypertension (CTEPH) is characterised by the persistence of organised thrombus, few pro-thrombotic risk factors have been identified in subjects with the disease. The aim of the present study was to compare the prevalence of eight functionally relevant haemostatic polymorphisms between CTEPH subjects and healthy controls. Genomic DNA was isolated from 214 CTEPH subjects and 200 healthy controls, and analysed for Factor V Leiden, prothrombin guanine (G) to adenine (A) substitution at nucleotide 20210 (20210G>A), plasminogen activator inhibitor-1 4G/5G, tissue plasminogen activator 7351 cytosine (C)>thymidine (T), Factor XIII 100G>T, fibrinogen Aα substitution of threonine with alanine at position 312 (Thr312Ala), fibrinogen Bβ substitution of arginine with lysine at position 448 (Arg448Lys) and fibrinogen Bβ 455G>A polymorphisms. A significant difference was demonstrated in fibrinogen Aα Thr312Ala genotype and allele frequencies between CTEPH subjects and controls. The presence of the alanine allele significantly increased the risk of CTEPH. The fibrinogen Aα alanine 312 allele alters fibrinogen α–α chain cross-linkage and has previously been associated with both increased risk of embolisation and increased resistance to thrombolysis. An association between this polymorphism and chronic thromboembolic pulmonary hypertension, therefore, supports an embolic aetiology for this disease, and may provide a mechanism by which thrombus persists following an acute event.