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Clinical Chemistry 0: 200302825, 2003; 10.1373/clinchem.2003.028258
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Received on October 10, 2003
Accepted on October 29, 2003

Lipids, Lipoproteins, and Cardiovascular Risk Factors

Genetic Effects on Baseline Values of C-Reactive Protein and Serum Amyloid A Protein: A Comparison of Monozygotic and Dizygotic Twins

Alex J. MacGregor 1, J. Ruth Gallimore 2, Tim D. Spector 1, Mark B. Pepys 2*

1 Twin Research and Genetic Epidemiology Unit, St. Thomas’ Hospital, London SE1 7EH, UK
2 Centre for Amyloidosis and Acute Phase Proteins, Department of Medicine, Royal Free Campus, Royal Free and University College Medical School, London NW3 2PF, UK

* To whom correspondence should be addressed. E-mail: m.pepys{at}rfc.ucl.ac.uk.

Background: C-Reactive protein (CRP) and serum amyloid A protein (SAA) are exquisitely sensitive acute-phase reactants, but their baseline values are surprisingly constant in individuals in the general population. These values, especially of CRP, are associated with future atherothrombotic events, and the determinants of baseline CRP and SAA concentration are therefore of considerable interest.

Methods: CRP and SAA concentrations were measured by well-validated automated microparticle capture enzyme immunoassays, standardized on the respective WHO International Reference Standards, in serum from 146 monozygotic and 164 dizygotic healthy female UK twin pairs from the general population, with mean (range) ages of 58.0 (40-69.6) and 55.7 (40-70.3) years, respectively, who were also very closely matched for height, weight, body mass index, blood pressure, and lifestyle variables. Statistical modeling based on variance components analysis was used to estimate the genetic contribution to the observed values.

Results: As reported previously, CRP values were associated with body mass index, smoking, and hormone replacement therapy. After exclusion of the few samples with CRP concentrations >10 mg/L, which indicate an ongoing acute-phase response rather than baseline values, and inclusion of adjustments for all known confounding variables, there was significantly higher correlation of CRP and SAA results among monozygotic than among dizygotic twins. The estimated hereditability (95% confidence interval) of baseline values was 52% (40-62%) for CRP and 59% (49-68%) for SAA.

Conclusion: There is a substantial genetic contribution to baseline serum concentrations of CRP and SAA.© 2004 American Association for Clinical Chemistry




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