title: The plasminogen activator inhibitor-1 gene, hypofibrinolysis, and osteonecrosis.
abstract: In 59 patients with osteonecrosis of the hip, four genes associated with thrombophilia or hypofibrinolysis along with coagulation tests were studied to determine the pathoetiologic associations of heritable coagulation disorders with osteonecrosis. Patients did not differ from healthy control subjects for the thrombophilic Factor V Leiden, prothrombin, or methylenetetrahydrofolate reductase mutations. The plasminogen activator inhibitor-1 gene was shifted toward homozygosity for the 4G polymorphism; 41% of patients with osteonecrosis were homozygous for the 4G/4G polymorphism versus 20% of 40 healthy control subjects. The gene product of the 4G polymorphism, hypofibrinolytic plasminogen activator inhibitor activity, was higher in patients than in control subjects (median 19.2 versus 6.3 U/mL); 61% of patients had high plasminogen activator inhibitor activity (> or = 16.4 U/mL) versus 5% of control subjects. Stimulated tissue plasminogen activator activity (inhibited by plasminogen activator inhibitor activity) was lower in patients than in control subjects (3.10 versus 5.98 IU/mL); 31% of patients had low stimulated tissue plasminogen activator activity (< 2.28 IU/mL) versus 3% of control subjects. Heritable hypofibrinolysis conferred by the 4G/4G mutation of the plasminogen activator inhibitor-1 gene seems to be a major pathoetiology of primary osteonecrosis.
authors.affiliation: Cholesterol Center, Jewish Hospital, Cincinnati, OH 45229, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Glueck
authors.forename: R N
authors.initials: RN
authors.lastname: Fontaine
authors.forename: R
authors.initials: R
authors.lastname: Gruppo
authors.forename: D
authors.initials: D
authors.lastname: Stroop
authors.forename: L
authors.initials: L
authors.lastname: Sieve-Smith
authors.forename: T
authors.initials: T
authors.lastname: Tracy
authors.forename: P
authors.initials: P
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D001780:Blood Coagulation Tests; D002648:Child; D005165:Factor V / Q000235:genetics; D005260:Female; D005342:Fibrinolysis / Q000235:genetics*; D006147:Guanine; D006621:Hip Joint / Q000473:pathology*; D006720:Homozygote; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D010020:Osteonecrosis / Q000235:genetics*; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics; D011516:Prothrombin / Q000235:genetics; D019851:Thrombophilia / Q000235:genetics*
chemical_list: D017395:Plasminogen Activator Inhibitor 1; C095381:factor V Leiden; D006147:Guanine; D005165:Factor V; D011516:Prothrombin; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)