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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Best
Lyle G
LG
Missouri Breaks Industries Research Inc, Timber Lake, SD, USA. sbest@utma.com
North
Kari E
KE
Tracy
Russell P
RP
Lee
Elisa T
ET
Howard
Barbara V
BV
Palmieri
Vittorio
V
Maccluer
Jean W
JW
D000368:Aged; D000704:Analysis of Variance; D002097:C-Reactive Protein / Q000235:genetics* / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000235:genetics / Q000378:metabolism; D005340:Fibrinogen / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D016013:Likelihood Functions; D008875:Middle Aged; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics* / Q000378:metabolism
D017395:Plasminogen Activator Inhibitor 1; D005340:Fibrinogen; D002097:C-Reactive Protein