CRP and FCGR2A genes have an epistatic effect on carotid artery intima‐media thickness: the Cardiovascular Risk in Young Finns Study |
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| Authors: | T. Pessi,C. Eklund,H. Huhtala,O. T. Raitakari,M. Juonala,M. K h nen,J. S. A. Viikari,T. Lehtim ki,M. Hurme |
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| Affiliation: | 1. Department of Microbiology and Immunology, Medical School, University of Tampere, Tempere, Finland,;2. 3. School of Public Health, University of Tampere, Tempere, Finland,;4. Department of Clinical Physiology, University of Turku, Turku, Finland,;5. Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland,;6. Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland,;7. Department of Medicine, University of Turku, Turku, Finland,;8. Department of Clinical Chemistry, Tampere University Hospital and University of Tampere, Tempere, Finland, and;9. Department of Microbiology and Immunology, Medical School, University of Tampere and Department of Microbiology, Tampere University Hospital, Tampere, Finland |
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| Abstract: | The role of the inflammatory mediator C‐reactive protein (CRP) in atherosclerosis is recognized although its specific functions are not entirely clear. CRP binds to the Fcγ receptor2A (FcγR2A) and its polymorphism, FCGR2A (Arg131His), strongly influences the binding. We wanted to evaluate the CRP‐mediated proatherogenic process on early atherosclerosis and investigated whether CRP and FCGR2A show an interactive effect on carotid intima‐media thickness (IMT). Polymorphisms of FCGR2A (Arg131His) and CRP (–717A > G, –286C > T > A, +1059G > C, +1444C > T and +1846G > A) were genotyped and their effects on IMT were analyzed in 2260 young adults participating in the Cardiovascular Risk in Young Finns Study. CRP haplotypes were constructed based on the CRP polymorphisms. The FCGR2A(Arg131His) polymorphism did not have an independent effect on IMT but a significant gene‐gene interaction, epistasis, between FCGR2A and CRP genetics on IMT was found. The epistatic effect was seen in men at haplotype and genotypic level; both CRP haplotype GCGCG (–717, –286, +1059, +1444 and +1846) and CRP–717A > G polymorphism interacted with FCGR2A(Arg131His) on IMT. After adjustment with classical risk factors the P‐values for interaction were P = 0.013 and P = 0.010, respectively. No associations were observed in women. In conclusion, this study showed that the effect of CRP genetics on early atherosclerotic changes is modulated by the FCGR2A genetics. |
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