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.

Both the Environment and Genes Are Important for Concentrations of Cadmium and Lead in Blood

“…Nevertheless There was a moderate association between BCd and BPb levels among nonsmokers that was entirely attributable to environmental influences. The lack of a genetic mediator for this covariation is notable and is in striking contrast to findings for components of the metabolic syndrome (37). The association is consistent with findings in children with environmental exposure to Cd and Pb (38,39).…”

Segregation Analysis of Plasminogen Activator Inhibitor-1 and Fibrinogen Levels in the NHLBI Family Heart Study

“…27 Several studies previously estimated the degree to which plasma PAI-1 level aggregates within families. Hong et al 28 reported a heritability of 42% for PAI-1 concentration in a study of 217 middle-aged and elderly twin pairs from Sweden. In a study of white European nuclear families, Henry et al 29 reported age-and gender-adjusted familial correlations for PAI-1 antigen level ranging from 0.21 to 0.23 in first-degree relatives but even higher correlations in spouse pairs (rϭ0.31).…”

Associação de níveis plasmáticos de PAI-1 e polimorfismo 4G/5G em pacientes com doença arterial coronariana

“…Plasma PAI-1 levels may be influenced by several factors 20 , among which genetic factors. Hong et al 21 showed that 42% of the variations found in plasma PAI-1 levels were due to genetic factors, in a study involving the Swedish population. Naram et al 11 , examining the South African population, observed that lower plasma PAI-1 levels were obtained for the black population compared with Caucasians.…”