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Nutritional Epidemiology

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^1,2,3

⁴ Department of Preventive Medicine and Public Health, School of Medicine, University of Valencia, 46010 Valencia, Spain ⁵ CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, 28029 Madrid, Spain ⁶ Human Nutrition Unit, Faculty of Medicine, University Rovira i Virgili, 43201 Reus, Spain ⁷ Department of Preventive Medicine and Public Health, School of Medicine, University of Navarra, 31080 Navarra, Spain ⁸ Cardiovascular Epidemiology Unit, Municipal Institut for Medical Research, 08003 Barcelona, Spain ⁹ Instituto de la Grasa, Consejo Superior de Investigaciones Cientificas, 41012 Sevilla, Spain ¹⁰ Department of Epidemiology, School of Medicine, University of Malaga, 49071 Malaga, Spain ¹¹ Department of Cardiology, Hospital Txagorritxu, 01009 Vitoria, Spain ¹² University Institute for Health Sciences Investigation, Hospital Son Dureta, 07014 Palma de Mallorca, Spain ¹³ Department of Epidemiology and Public Health, Hospitales Universitarios Virgen del Rocío, 41013 Sevilla, Spain ¹⁴ Department of Family Medicine, San Pablo Health Center, Primary Care Division of Sevilla, 41007 Sevilla, Spain ¹⁵ Department of Biochemistry and Molecular Biology, University of Valencia, 46010 Valencia, Spain ¹⁶ Department of Nutrition and Bromatology, School of Pharmacy, 08007 Barcelona, Spain ¹⁷ Arteriosclerosis Unit, Hospital Carlos III, 28029 Madrid, Spain ¹⁸ Primary Health Care Division, 08036 Barcelona, Spain; and ¹⁹ Lipid Clinic, Endocrinology and Nutrition Service, and ²⁰ Department of Internal Medicine, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi Sunyer, 08036 Barcelona, Spain

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 µg/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.

^* To whom correspondence should be addressed. E-mail: dolores.corella{at}uv.es.

Manuscript received 21 May 2008. Initial review completed 20 June 2008. Revision accepted 21 October 2008.