British Journal of Nutrition

Full Papers

Molecular Nutrition

The Mediterranean diet protects against waist circumference enlargement in 12Ala carriers for the PPARγ gene: 2 years' follow-up of 774 subjects at high cardiovascular risk

Cristina Razquina1, J. Alfredo Martineza1, Miguel A. Martinez-Gonzaleza2, Dolores Corellaa3, José Manuel Santosa4 and Amelia Martia1 c1

a1 Department of Nutrition and Food Sciences, Physiology and Toxicology, University of Navarra, Irunlarrea 1, 31080 Pamplona, Navarra, Spain

a2 Department of Preventive Medicine and Public Health, School of Medicine–Clinica Universitaria, University of Navarra, Spain

a3 Department of Preventive Medicine, School of Medicine, University of Valencia, Spain

a4 Department of Family Medicine, San Pablo Health Centre and CIBER Fisiopatología Obesidad y Nutrición (CB06/03), Instituto de Salud Carlos III, Spain


The PPARγ gene regulates insulin sensitivity and adipogenesis. The Pro12Ala polymorphism of this gene has been related to fat accumulation. Our aim was to analyse the effects of a 2-year nutritional intervention with Mediterranean-style diets on adiposity in high-cardiovascular risk patients depending on the Pro12Ala polymorphism of the PPARγ gene. The population consisted of a substudy (774 high-risk subjects aged 55–80 years) of the Prevención con Dieta Mediterránea (PREDIMED) randomised trial aimed at assessing the effect of the Mediterranean diet for CVD prevention. There were three nutritional intervention groups: two of them of a Mediterranean-style diet and the third was a control group advised to follow a conventional low-fat diet. All the participants were genotyped by PCR-restriction fragment length polymorphism (RFLP). The results showed that carriers of the 12Ala allele allocated to the control group had a statistically significant higher change in waist circumference (adjusted difference coefficient = 2·37 cm; P = 0·014) compared with wild-type subjects after 2 years of nutritional intervention. This adverse effect was not observed among 12Ala carriers allocated to both Mediterranean diet groups. In diabetic patients a statistically significant interaction between Mediterranean diet and the 12Ala allele regarding waist circumference change was observed ( − 5·85 cm; P = 0·003). In conclusion, the Mediterranean diet seems to be able to reduce waist circumference in a high-cardiovascular risk population, reversing the negative effect that the 12Ala allele carriers of the PPARγ gene appeared to have. The beneficial effect of this dietary pattern seems to be higher among type 2 diabetic subjects.

(Received September 19 2008)

(Revised January 07 2009)

(Accepted January 26 2009)

(Online publication March 09 2009)


c1 Corresponding author: Professor Amelia Marti, fax +34 948 42 56 49, email


Abbreviations: PREDIMED, Prevención con Dieta Mediterránea