title: Moderate genetic influences on plasma levels of plasminogen activator inhibitor-1 and evidence of genetic and environmental influences shared by plasminogen activator inhibitor-1, triglycerides, and body mass index.
abstract: Both genes and environmental factors have been reported to influence plasma levels of plasminogen activator inhibitor-1 (PAI-1). However, the relative importance of genetic influences (i.e., heritability) on plasma PAI-1 levels has not yet been investigated. Furthermore, PAI-1 levels are correlated with body mass index (BMI) and triglycerides. These correlations could reflect genetic and/or environmental factors in common to PAI-1, triglycerides, and BMI. We applied multivariate genetic analysis methods to assess the relative importance of genetic and environmental influences on plasma PAI-1 levels and to test the significance of genetic and/or environmental influences shared by PAI-1, triglycerides, and BMI in 217 pairs of middle-aged and elderly twins, of whom 113 pairs were reared apart and 121 pairs were women. The heritability estimate for PAI-1 levels was 42%. Individual-specific environmental factors explained 36% of the variance for PAI-1 levels. The remaining variance of PAI-1 was explained by rearing and residual-familial environmental factors. Furthermore, a genetic correlation of 1.00 between PAI-1 and triglycerides, a rearing environmental correlation of 1.00 between PAI-1 and BMI, a residual-familial environmental correlation of 1.00 between PAI-1 and triglycerides, and a genetic correlation of 0.63 between PAI-1 and BMI, were found. In conclusion, the present results suggest that genetic influences on plasma PAI-1 are moderate. Genetic and shared rearing or residual-familial environmental factors shared by PAI-1, BMI, and triglycerides explain the phenotypic association between these measures. It appears that all the genetic influences for PAI-1 are more or less shared with those for triglycerides and BMI.
authors.affiliation: Division of Cardiovascular and Genetic Epidemiology, Karolinska Institute, Stockholm, Sweden. yuling@wubios.wustl.edu
authors.forename: Y
authors.initials: Y
authors.lastname: Hong
authors.forename: N L
authors.initials: NL
authors.lastname: Pedersen
authors.forename: N
authors.initials: N
authors.lastname: Egberg
authors.forename: U
authors.initials: U
authors.lastname: de Faire
mesh_terms: D000300:Adoption; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D015331:Cohort Studies; D004198:Disease Susceptibility; D004200:Diseases in Twins / Q000453:epidemiology / Q000235:genetics; D004777:Environment; D005260:Female; D006801:Humans; D015228:Hypertriglyceridemia / Q000235:genetics; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009765:Obesity / Q000235:genetics; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D014280:Triglycerides / Q000097:blood*; D014427:Twins / Q000235:genetics*; D014429:Twins, Dizygotic / Q000235:genetics; D014430:Twins, Monozygotic / Q000235:genetics
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D014280:Triglycerides