The interleukin-6 –174 G/C promoter polymorphism and arterial stiffness; the Rotterdam Study

Original Research

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Authors: Mark PS Sie, Francesco US Mattace-Raso, André G Uitterlinden, Pascal P Arp, Albert Hofman, et al

Published Date September 2008 Volume 2008:4(4) Pages 863 - 869

DOI: http://dx.doi.org/10.2147/VHRM.S1693

Mark PS Sie¹, Francesco US Mattace-Raso², André G Uitterlinden², Pascal P Arp², Albert Hofman¹, Huibert AP Pols², Arnold PG Hoeks³, Robert S Reneman⁴, Roland Asmar⁵, Cornelia M van Duijn¹, Jacqueline CM Witteman¹

¹Department of Epidemiology and Biostatistics, ²Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands; ³Department of Biophysics, ⁴Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands; ⁵Cardiovascular Institute, Paris, France

Abstract: Arterial stiffness normally increases with age and has been established as a precursor of cardiovascular disease. Interleukin-6 is a pleiotropic inflammatory cytokine with an important role in the inflammatory cascade, such as up-regulation of C-reactive protein (CRP). The interleukin-6 –174-G/C promoter polymorphism appears to infl uence levels of inflammatory markers, which have been shown to be associated with arterial stiffness. We studied the association of this polymorphism with levels of interleukin-6 and CRP and with arterial stiffness. The study (n = 3849) was embedded in the Rotterdam Study, a prospective, population-based study. Analyses on the association between the –174-G/C polymorphism and pulse wave velocity, distensibility coefficient, and pulse pressure were performed using analyses of variance. Analyses on the levels of inflammatory markers and arterial stiffness were performed using linear regression analyses. Analyses were adjusted for age, sex, mean arterial pressure, heart rate, known cardiovascular risk factors, and atherosclerosis. We found pulse wave velocity to be 0.35 m/s higher for CC-homozygotes vs. wildtype GG-homozygotes (p = 0.018) with evidence for an allele-dose effect (p trend = 0.013), and a similar pattern for pulse pressure (p trend = 0.041). No apparent consistent association with the distensibility coefficient was found. CRP levels were associated with pulse wave velocity (p = 0.007). In conclusion, the interleukin-6 –174 G/C polymorphism is associated with increased arterial stiffness and pulse pressure.

Keywords: IL-6, CRP, arterial stiffness, pulse wave velocity, distensibility coefficient, pulse pressure

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