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 conc entrations are risk factors for coronary heart disease. We investigate d environmental, familial, and genetic influences on PAI-1 antigen and fibrinogen concentrations in 2029 adults from 512 randomly ascertaine d families in 4 US communities. We used maximum-likelihood segregation analysis to fit several genetic and nongenetic modes of inheritance t o the data to determine whether mendelian inheritance of a major gene could best explain The familial distributions of these 2 hemostatic fa ctors. Age- and gender-adjusted familial correlations for PAI-1 antige n 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 indicate d a major gene associated with higher PAI-1 concentrations in 65% of i ndividuals from these families. Demographic, anthropometric, lifestyle , and metabolic characteristics together explained 37% to 47% of the v ariation in PAI-1 antigen levels, and the inferred major gene explaine d an additional 17% of the variance. Positive and statistically signif icant age- and gender-adjusted familial correlations in first-degree r elatives indicated a possible heritable component influencing plasma f ibrinogen concentration (r=0.17, 95% CI=0.13 to 0.22); however, segreg ation analysis did not provide statistical evidence of a major gene co ntrolling fibrinogen level. These family data suggest that there are m odest familial and genetic effects on the concentration of PAI-1.