Segregation analysis of plasminogen activator inhibitor-1 and fibrinogen levels in the NHLBI family heart study.
Elevated plasminogen activator inhibitor-1 (PAI-1) and fibrinogen concentrations are risk factors for coronary heart disease. We investigated environmental, familial, and genetic influences on PAI-1 antigen and fibrinogen concentrations in 2029 adults from 512 randomly ascertained families in 4 US communities. We used maximum-likelihood segregation analysis to fit several genetic and nongenetic modes of inheritance to the data to determine whether mendelian inheritance of a major gene could best explain the familial distributions of these 2 hemostatic factors. Age- and gender-adjusted familial correlations for PAI-1 antigen level averaged 0.16 in first-degree relatives (95% CI=0.11 to 0.21); the spouse correlation was positive but not statistically significant (r=0.10, 95% CI=-0.02 to 0.23). Complex segregation analysis indicated a major gene associated with higher PAI-1 concentrations in 65% of individuals from these families. Demographic, anthropometric, lifestyle, and metabolic characteristics together explained 37% to 47% of the variation in PAI-1 antigen levels, and the inferred major gene explained an additional 17% of the variance. Positive and statistically significant age- and gender-adjusted familial correlations in first-degree relatives indicated a possible heritable component influencing plasma fibrinogen concentration (r=0. 17, 95% CI=0.13 to 0.22); however, segregation analysis did not provide statistical evidence of a major gene controlling fibrinogen level. These family data suggest that there are modest familial and genetic effects on the concentration of PAI-1.
Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, NC 27514, USA. jim_pankow@unc.edu
J S
JS
Pankow
A R
AR
Folsom
M A
MA
Province
D C
DC
Rao
R R
RR
Williams
J
J
Eckfeldt
T A
TA
Sellers
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005260:Female; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009316:National Institutes of Health (U.S.); D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D014481:United States
D017395:Plasminogen Activator Inhibitor 1; D005340:Fibrinogen