Gene polymorphisms of tissue plasminogen activator and plasminogen activator inhibitor-1 in patients with antiphospholipid antibodies.
OBJECTIVE
Impaired fibrinolytical outcomes may be one of the pathogenic factors for thrombotic events in patients with antiphospholipid antibodies (aPL). We investigated the consequences of the gene polymorphisms of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) in patients positive for aPL.


METHODS
Seventy-seven Japanese and 82 British patients with aPL were examined for Alu-repeat insertion (I)/deletion (D) polymorphism of the tPA gene by polymerase chain reaction (PCR), and 4G/5G polymorphism in the PAI-1 promoter gene by site-directed mutagenesis-PCR and restriction fragment length polymorphism analysis. Correlations between these polymorphisms and clinical symptoms of antiphospholipid syndrome (APS) (arterial thrombosis, venous thrombosis, miscarriage) were analyzed.


RESULTS
Significant differences in the allele frequencies of these genes did not exist between patients and controls. There was no significant correlation between these gene polymorphisms and clinical symptoms of APS in patients with aPL.


CONCLUSIONS
Polymorphisms of the tPA or PAI-1 genes probably do not significantly influence the risk of anerial thrombosis, venous thrombosis, or pregnancy morbidity in patients with aPL.
Yasuda
Shinsuke
S
Department of Medicine II, Hokkaido University School of Medicine, Sapporo, Japan.
Tsutsumi
Akito
A
Atsumi
Tatsuya
T
Bertolaccini
Maria L
ML
Ichikawa
Kenji
K
Khamashta
Munther A
MA
Hughes
Graham R V
GR
Koike
Takao
T
D000483:Alleles; D000704:Analysis of Variance; D017152:Antibodies, Antiphospholipid / Q000032:analysis; D016736:Antiphospholipid Syndrome / Q000208:ethnology / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D015999:Multivariate Analysis; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011336:Probability; D012016:Reference Values; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D010959:Tissue Plasminogen Activator / Q000235:genetics*; D044465:White People / Q000235:genetics*
D017152:Antibodies, Antiphospholipid; D017395:Plasminogen Activator Inhibitor 1; D010959:Tissue Plasminogen Activator