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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:316-320.)
© 1999 American Heart Association, Inc.

Original Contributions

Determinants of Plasma Levels of Plasminogen Activator Inhibitor-1

A Study of Normotensive Twins

Maurizio Cesari; Maria Teresa Sartori; Giovanni M. Patrassi; Silvia Vettore; Gian Paolo Rossi

From the Department of Clinical and Experimental Medicine, Clinica Medica 4 (M.C., G.P.R.) and Institute of Medical Semiotics, II Chair of Internal Medicine, University of Padua Medical School (M.T.S., G.M.P., S.V.), Italy.

Correspondence to G.P. Rossi, MD, FACC, Clinica Medica 4, Department of Clinical and Experimental Medicine, University Hospital, Via Giustiniani, 2, 35126 Padova, Italy. E-mail gprossi{at}ux1.unipd.it

Abstract—We investigated whether plasma levels of the plasminogen activator inhibitor type 1 antigen (PAI-1:Ag) are genetically determined in monozygotic (MZ) and dizygotic (DZ) twins. Twenty-five pairs of healthy twins underwent measurements of PAI-1:Ag and other variables, including body mass index, mean blood pressure, plasma renin activity, insulin, and glucose. To ascertain the zygosity of twins, highly discriminating micro- and minisatellite systems with variable numbers of tandem repeats were analyzed by PCR amplification followed by polyacrylamide gel electrophoresis. Subjects were also genotyped for the 4G/5G polymorphism by PCR. Estimates of genetic variance and heritability were obtained for PAI-1:Ag, and for body mass index, mean blood pressure, plasma renin activity, glucose, and insulin by jointly examining data in a path analysis with TWINAN90. Results showed that 12 pairs of twins were MZ and 13 were DZ. All tests of genetic variance [within pair (WP): F=6.24, P=0.002; among component (AC): F=2.62, P=0.04; average absolute difference t test=3.00, P=0.004] showed significant genetic variance of PAI-1:Ag, but not of the other variables. Three tests of heritability (WP=0.837, P=0.002; AC=1.791, P<0.05; intraclass correlation: 1.180, P=0.001) consistently showed significant PAI-1:Ag heritability. Additive genetic influences (A), dominance genetic effect (D), and random environmental influences (E) accounted for 0.714, 0.154, and 0.132 of PAI-1:Ag variance, respectively. No effect of different 4G/5G genotypes was found. Thus, these results show significant genetic variance and heritability of PAI-1:Ag and suggest that A is more important than both D and E in determining PAI-1:Ag variance.

Key Words: plasminogen activator inhibitor type 1 • fibrinolysis • gene polymorphism • twins • humans

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