European Heart Journal Advance Access originally published online on October 22, 2007
European Heart Journal 2008 29(10):1250-1258; doi:10.1093/eurheartj/ehm442
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DNA variants, plasma levels and variability of C-reactive protein in myocardial infarction survivors: results from the AIRGENE study
1 GSF National Research Center for Environment and Health, Institute of Epidemiology, Neuherberg, Germany
2 Department of Internal Medicine II—Cardiology, University of Ulm Medical Centre, Robert-Koch Strasse 8, D-89081 Ulm, Germany
3 Institute of Medical Information Processing, Biometry and Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany
4 Catholic University, Rome, Italy
5 Department of Statistics, Ludwig-Maximilians-Universität, Munich, Germany
6 Department of Hygiene and Epidemiology, University of Athens Medical School, Athens, Greece
7 Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden
8 Department of Epidemiology and Health Promotion, National Public Health Institute (KTL), Helsinki, Finland
9 Environmental Epidemiology Research Centre (CREAL), Institute Municipal Investigació Mèdica (IMIM), Barcelona, Spain
Received 21 February 2007; revised 7 September 2007; accepted 13 September 2007; online publish-ahead-of-print 22 October 2007.
* Corresponding author. Tel: +49 731 500 45001, Fax: +49 731 500 45021. Email: wolfgang.koenig{at}uniklinik-ulm.de
Aims: C-reactive protein represents the classical acute-phase protein produced in the liver in response to inflammatory stimuli. This study evaluated the association of gene polymorphisms with differences in C-reactive protein concentrations and assessed its intra-individual variability as a marker of individual response.
Methods and results: One thousand and three myocardial infarction (MI) survivors were recruited in six European cities, and C-reactive protein concentrations were measured repeatedly during a 6-month period. We investigated 114 polymorphisms in 13 genes, all involved in the innate inflammatory pathway. We found two polymorphisms within the C-reactive protein (CRP) gene rs1800947 and rs1205, of which the minor alleles were strongly associated with lower levels of C-reactive protein (P < 10–6). A haplotype, identified by those two polymorphisms, was associated with the lowest C-reactive protein concentrations (P < 10–6). Additionally, the minor alleles of several variants were significantly associated with greater individual variability of C-reactive protein concentrations (P < 10–3).
Conclusion: The present study investigated the association of polymorphisms with inter- and intra-individual variability of C-reactive protein levels. Two minor alleles of C-reactive protein variants were associated with lower C-reactive protein concentrations. Regarding intra-individual variability, we observed associations with the minor alleles of several variants in selected candidate genes, including the CRP gene itself.
Key Words: Epidemiology • Inflammation • Genetics • C-reactive protein • Myocardial infarction