Genetic variation in the C-reactive protein gene and arterial stiffness: The Rotterdam Study

Sie, M.P.S.; Mattace-Raso, F.U.S.; Kardys, I.; de Maat, M.P.M.; Uitterlinden, A.G.; Hofman, A.; Hoeks, A.P.G.; Reneman, R.S.; Asmar, R.; van Duijn, C.M.; Witteman, J.C.M.

doi:10.1016/j.artres.2008.10.002

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Volume 2, Issue 4 , Pages 148-155, November 2008

Genetic variation in the C-reactive protein gene and arterial stiffness: The Rotterdam Study

M.P.S. Sie
- Department of Epidemiology & Biostatistics, Erasmus Medical Center, P.O. Box 2040, 3000 CA Rotterdam, the Netherlands
- Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands
F.U.S. Mattace-Raso
- Department of Epidemiology & Biostatistics, Erasmus Medical Center, P.O. Box 2040, 3000 CA Rotterdam, the Netherlands
- Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands
I. Kardys
- Department of Epidemiology & Biostatistics, Erasmus Medical Center, P.O. Box 2040, 3000 CA Rotterdam, the Netherlands
M.P.M. de Maat
- Department of Haematology, Erasmus Medical Center, Rotterdam, the Netherlands
A.G. Uitterlinden
- Department of Epidemiology & Biostatistics, Erasmus Medical Center, P.O. Box 2040, 3000 CA Rotterdam, the Netherlands
- Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands
A. Hofman
- Department of Epidemiology & Biostatistics, Erasmus Medical Center, P.O. Box 2040, 3000 CA Rotterdam, the Netherlands
A.P.G. Hoeks
- Department of Biophysics (A.P.G.H.), Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands
R.S. Reneman
- Departments of Physiology (R.S.R.), Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands
R. Asmar
- Cardiovascular Institute, Paris, France
C.M. van Duijn
- Department of Epidemiology & Biostatistics, Erasmus Medical Center, P.O. Box 2040, 3000 CA Rotterdam, the Netherlands
J.C.M. Witteman
- Department of Epidemiology & Biostatistics, Erasmus Medical Center, P.O. Box 2040, 3000 CA Rotterdam, the Netherlands
- Corresponding author. Tel.: +31 10 708 7488; fax: +31 10 708 9382.

Received 30 May 2008; received in revised form 13 October 2008; accepted 16 October 2008. published online 25 November 2008.

Summary

Background and aim

Arterial stiffness increases with age and has been found to predict cardiovascular disease. C-reactive protein (CRP) is an inflammation marker and has been found to be associated with arterial stiffness and risk of cardiovascular disease. Genetic factors account for part of the variance in CRP level. We studied the association of the total common variation in the CRP gene by polymorphisms 1184 C/T, 2042 C/T, 2911 C/G and haplotypes with arterial stiffness within the Rotterdam study.

Methods

The study (n=3615) was embedded in the Rotterdam Study, a prospective, population-based study among subjects aged 55years and older. Associations of genotypes and haplotypes with CRP level and measures of arterial stiffness were examined using linear regression and analyses of variance. Measures of arterial stiffness included aortic pulse wave velocity, carotid distensibility and pulse pressure. Analyses were adjusted for age, sex, mean arterial pressure, heart rate, known cardiovascular risk factors and measures of atherosclerosis.

Results

CRP level was significantly associated with pulse wave velocity (p<0.001) and pulse pressure (p<0.05), also after adjusting for cardiovascular risk factors. CRP level was also associated with the 1184 C/T (T-allele: higher level), the 2042 C/T (T-allele: lower level) and 2911 C/G (G-allele: higher level) polymorphisms (all p<0.001). Genotype and haplotype analyses showed no consistent associations of genetic variation with pulse wave velocity, carotid distensibility and pulse pressure.

Conclusions

No consistent associations of the CRP polymorphisms 1184 C/T, 2042 C/T, 2911 C/G and corresponding haplotypes were found with measures of arterial stiffness.

Keywords: C-reactive protein, Polymorphism, Arterial stiffness, Pulse wave velocity, Distensibility coefficient, Pulse pressure