American Journal of Epidemiology Advance Access published online on July 19, 2007
American Journal of Epidemiology, doi:10.1093/aje/kwm151
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Original Contribution |
Variants in the CRP Gene as a Measure of Lifelong Differences in Average C-Reactive Protein Levels
The Cardiovascular Risk in Young Finns Study, 1980–2001
1 Department of Epidemiology and Public Health, Faculty of Biomedical Sciences, University College London, London, United Kingdom
2 Finnish Institute of Occupational Health, Helsinki, Finland
3 Department of Social Medicine, Faculty of Medicine and Dentistry, University of Bristol, Bristol, United Kingdom
4 Department of Microbiology and Immunology, Faculty of Medicine, University of Tampere, Tampere, Finland
5 Laboratory Centre, Tampere University Hospital, Tampere, Finland
6 Department of Clinical Chemistry, Tampere University Hospital and University of Tampere, Tampere, Finland
7 Department of Medicine, Faculty of Medicine, University of Turku, Turku, Finland
8 Department of Clinical Physiology, Faculty of Medicine, University of Turku, Turku, Finland
Correspondence to Prof. Mika Kivimäki, Department of Epidemiology and Public Health, University College London, 1-19 Torrington Place, London WC1E 6BT, United Kingdom (e-mail: m.kivimaki{at}ucl.ac.uk).
Received for publication February 7, 2007. Accepted for publication April 23, 2007.
Genetic association studies have used variants in the C-reactive protein (CRP) gene to estimate causal effects of lifelong circulating CRP levels on disease endpoints. However, the extent to which the genetic variants are actually associated with lifelong circulating CRP levels has not been demonstrated empirically. In a population-based prospective cohort study (1980–2001) of 1,609 young Finns (768 men and 841 women), the authors genotyped five single nucleotide polymorphisms in the CRP gene (–717A/G, –286C/T/A, +1059G/C, +1444T/C, and +1846G/A) and assessed circulating CRP levels at ages 3–18 years and 24–39 years. The haplotypes from the five single nucleotide polymorphisms were associated with circulating CRP levels in childhood and adulthood, with the strongest effect being found for average CRP level across these two measures taken at two time points in the life course. In combination, the haplotype pairs accounted for 3.9%, 3.3%, and 5.0% of the variation in circulating CRP levels in childhood, in adulthood, and for the mean of CRP levels at both time points, respectively. These findings support the assumption that the above genetic variants define groups with long-term differences in circulating CRP levels.
C-reactive protein; haplotypes; random allocation; variation (genetics)
Abbreviations: CRP, C-reactive protein; SNP, single nucleotide polymorphism
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