122 MODULATION BY THE MEDITERRANEAN DIET OF THE ASSOCIATIONS BETWEEN RAPGEF1 AND NEGR1 POLYMORPHISMS AND BLOOD PRESSURE IN A HIGH CARDIOVASCULAR RISK MEDITERRANEAN POPULATION

Abstract

Aims: To analyze the effect of relevant polymorphisms in novel genes on blood pressure in a high cardiovascular risk Mediterranean population as well as to study the gene-diet interactions between these genes and the adherence to the Mediterranean diet (MeDiet) in determining systolic (SBP) and diastolic blood pressure (DBP). We focused on the Rap guanine nucleotide exchange factor 1 (RAPGEF1) and on the neuronal growth regulator 1 (NEGR1) genes. RAPGEF1 encodes an exchange factor involved in cell signalling. NEGR1 may function as a trans-neural growth-promoting factor in the brain., Methods: We studied 1050 high cardiovascular risk (average age: 67+/-6 years) subjects with either type 2 diabetes, or at least 3 of the established cardiovascular risk factors: smoking, hypertension, hyperlipidemia, overweight, and family history of premature cardiovascular disease participating in the PREDIMED (PREvencion Dieta MEDiterranea)-Valencia Study. Clinical, biochemical and lifestyle variables were obtained. Adherence to the MeDiet was assessed by a recently validated 14-point MeDiet Adherence Screener. Polymorphisms in RAPGEF1 (rs7034356, rs4740294) and NEGR1 (rs2815752, rs3101336 and rs2568958) were determined., Results and conclusions: We observed statistically significant associations between RAPGEF1 and NEGRE1 polymorphisms and blood pressure. The mayor allele of the rs3101336 in NEGR1 (45%GG, 42%GA and 13%AA) was associated (p<0.05) with increased SBP (147+/-20, 147+/-20 and 143+/-20 mmHg) and DBP (84+/-11, 82+/-11 and 97+/-10 mmHg) in the whole population. However we found a statistically significant interaction (P=0.03) with the MeDiet. When the adherence to the MeDiet was high, the increasing effect of the G allele on blood pressure was abolished., (C) 2012 Lippincott Williams & Wilkins, Inc.