Genetic determination of acute phase reactant levels: the strong heart study

C-reactive protein (CRP), fibrinogen and plasminogen activating inhibitor-1 (PAI-1) are acute phase reactants (APRs); and high levels are indicative of physiologic inflammatory responses. Basal (non-stimulated) APR levels have also been shown to predict atherosclerotic complications in a number of populations. We sought to determine the relative contributions of genetic and environmental factors influencing basal serum levels of APRs.

This study used univariate quantitative genetic analyses to partition the phenotypic variance of these APRs into their additive genetic and environmental components using maximum likelihood variance decomposition methods. Bivariate analyses were done to detect genetic correlation between APRs. The computer program SOLAR was used to perform these analyses.

The Strong Heart Study (SHS) includes information on approximately 1,294 American Indian relative pairs. The proportion of variance due to environmental and acquired covariates affecting these APRs was modest, ranging from 16-20%. The proportion of variance due to genetic factors (heritability) ranged from 24-46%. In addition, there were significant genetic correlations between CRP/fibrinogen (rho=0.41 +/- 0.12) and CRP/PAI-1 (rho=0.46 +/- 0.19); but not between fibrinogen/PAI-1.

In the SHS cohort, the levels of APRs are determined to a substantial degree by genetic influences, and CRP shares common genetic determinants with fibrinogen and PAI-1.