Polymorphisms cyclooxygenase-2 -765G>C and interleukin-6 -174G>C are associated with serum inflammation markers in a high cardiovascular risk population and do not modify the response to a Mediterranean diet supplemented with virgin olive oil or nuts

J Nutr. 2009 Jan;139(1):128-34. doi: 10.3945/jn.108.093054. Epub 2008 Dec 3.


Inflammation is involved in cardiovascular diseases. Some studies have found that the Mediterranean diet (MD) can reduce serum concentrations of inflammation markers. However, none of these studies have analyzed the influence of genetic variability in such a response. Our objective was to study the effect of the -765G>C polymorphism in the cyclooxygenase-2 (COX-2) gene and the -174G>C polymorphism in the interleukin-6 (IL-6) gene on serum concentrations of IL-6, C-reactive protein, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule-1 as well as their influence on the response to a nutritional intervention with MD. An intervention study in a high cardiovascular risk Mediterranean population (314 men and 407 women) was undertaken. Participants were randomly assigned to consume a low-fat control diet or a MD supplemented with virgin olive oil or nuts. Measures were obtained at baseline and after a 3-mo intervention period. At baseline, the COX-2 -765G>C polymorphism was associated with lower serum IL-6 (5.85 +/- 4.82 in GG vs. 4.74 +/- 4.14 ng/L in C-allele carriers; P = 0.002) and ICAM-1 (265.8 +/- 114.8 in GG vs. 243.0 +/- 107.1 microg/L in C-carriers; P = 0.018) concentrations. These differences remained significant after multivariate adjustment. The IL-6 -174G>C polymorphism was associated with higher (CC vs. G-carriers) serum ICAM-1 concentrations in both men and women and with higher serum IL-6 concentrations in men. Following the dietary intervention, no significant gene x diet interactions were found. In conclusion, although COX-2 -765G>C and IL-6 -174G>C polymorphisms were associated with inflammation, consuming a MD (either supplemented with virgin olive oil or nuts) reduced the concentration of inflammation markers regardless of these polymorphisms.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood
  • C-Reactive Protein / analysis
  • Cardiovascular Diseases / diet therapy
  • Cardiovascular Diseases / prevention & control*
  • Cyclooxygenase 2 / genetics*
  • Diet, Mediterranean*
  • Female
  • Gene Expression Regulation / physiology
  • Humans
  • Inflammation / blood
  • Intercellular Adhesion Molecule-1 / blood
  • Interleukin-6 / blood
  • Interleukin-6 / genetics*
  • Male
  • Middle Aged
  • Nuts*
  • Olive Oil
  • Plant Oils*
  • Polymorphism, Genetic
  • Vascular Cell Adhesion Molecule-1 / blood


  • Biomarkers
  • Interleukin-6
  • Olive Oil
  • Plant Oils
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • C-Reactive Protein
  • Cyclooxygenase 2