Determinants of plasma levels of plasminogen activator inhibitor-1 : A study of normotensive twins.
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.
Cesari
M
M
Department of Clinical and Experimental Medicine, Clinica Medica 4, Padova, Italy.
Sartori
M T
MT
Patrassi
G M
GM
Vettore
S
S
Rossi
G P
GP
D000328:Adult; D001794:Blood Pressure / Q000502:physiology; D004777:Environment; D005799:Genes, Dominant / Q000502:physiology; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood* / Q000235:genetics*; D012016:Reference Values; D014429:Twins, Dizygotic / Q000235:genetics; D014430:Twins, Monozygotic / Q000235:genetics