Influence of the Alu-repeat I/D polymorphism in t-PA gene intron 8 on the stimulated t-PA release after venous occlusion.
Tissue type plasminogen activator (t-PA) is released from endothelium in both a constitutive and regulated fashion. In healthy subjects, an association between net t-PA release rate and a few t-PA gene polymorphisms, including the Alu-repeat I/D polymorphism in intron 8, was described. The possible influence of the Alu-repeat polymorphism on t-PA release was evaluated after a venous occlusion test (VO) in 82 patients showing an impaired fibrinolytic capacity associated with different arterial disease or with previous venous thrombosis, and in 50 healthy controls. Euglobulin lysis time, t-PA antigen (t-PA:Ag) and activity, PAI-1 antigen and activity plasma levels were assayed before and 20 minutes after VO; the Alu-repeat I/D polymorphism was determined by PCR. Defective fibrinolysis was due to reduced t-PA release in 40 patients (t-PA group) and to PAI-1 excess in 42 patients (PAI group). No differences in both genotype distribution and allele frequencies were observed between patients and controls. The t-PA:Ag increase after VO (20/0-minute levels ratio adjusted for hematocrit) was considerably higher both in controls and in PAI group patients carrying the I allele than in the DD genotype carriers (II, ID, DD: 3.77+/-0.62, 3.43+/-0.44, 2.06+/-0.32 in controls, and 3.67+/-0.23, 2.80+/-0.50, 1.62+/-0.29 in PAI group, respectively). The difference was significant between the DD and both the ID and II genotypes in controls (p<0.05), and between the DD and II genotypes in PAI-1 group (p<0.05). A slight and nonsignificant trend of association between genotype and t-PA:Ag 20/0 ratio was seen in the t-PA group patients. In conclusion, these data suggest a possible genetic modulation of t-PA-regulated secretion.
Sartori
Maria Teresa
MT
Department of Medical and Surgical Sciences, University of Padua Medical School, Padova, Italy. mtsart@unipd.it
Saggiorato
Graziella
G
Spiezia
Luca
L
Varvarikis
Costantino
C
Carraro
Gianni
G
Patrassi
Giovanni Maurizio
GM
Girolami
Antonio
A
D000328:Adult; D020087:Alu Elements / Q000235:genetics*; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D005838:Genotype; D006801:Humans; D007438:Introns; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D012016:Reference Values; D010959:Tissue Plasminogen Activator / Q000235:genetics*; D020246:Venous Thrombosis / Q000235:genetics*
D017931:DNA Primers; D017395:Plasminogen Activator Inhibitor 1; D010959:Tissue Plasminogen Activator