C358A Polymorphism of the Endocannabinoid Degrading Enzyme Fatty Acid Amide Hydrolase (FAAH) Influence On Metabolic Parameters a High Protein/Low Carbohydrate versus a Standard Hypocaloric Diet

Background and aim: The C385A polymorphism of FAAH gene (rs324420C>A) has been associated with obesity. We investigate the role of this polymorphism on cardiovascular risk factors and weight loss secondary to a high protein/ low carbohydrate vs. a standard hypocaloric diets (1000 kcal/day) during 9 months. Methods: A sample of 284 subjects with obesity (body mass index (BMI) >30) was enrolled. These subjects were randomly allocated to one of two diets for a period of nine months Diet S (standard protein hypocaloric diet) vs. Diet HP (high protein-low carbohydrate hypocaloric diet). Results: After both diets and in both genotype groups (CC vs. CA+AA), body mass index (BMI), weight, fat mass, waist circumference and systolic blood pressure decreased. With the diet type HP and in non A carriers, glucose (-5.3 ± 1.2 mg/dl vs. -1.8 ± 2.1 mg/dl; p<0.05), insulin levels (-3.1 ± 1.9UI/L vs. -1.1 ± 2.0 UI/L; p<0.05), HOMA-R (-0.9 ± 0.8 units vs. -0.3 ± 1.0 units; p<0.05), total cholesterol (-11.9 ± 8.2 mg/dl vs. -0.1 ± 3.1mg/dl; p<0.05), and LDLtotal cholesterol (-9.8 ± 4.2 mg/dl vs. -1.0 ± 2.1mg/dl; p<0.05) decreased. After diet S and in patients with both genotypes, total cholesterol (-6.0 ± 3.1 mg/dl vs. -10.0 ± 8.2mg/dl; ns), triglycerides (-8.1 ± 7.1 mg/dl vs. -13.1 ± 8.9 mg/dl; ns) and LDLtotal cholesterol (-5.9 ± 3.0 mg/dl vs. -9.1 ± 5.8mg/dl; p<0.05) decreased. Conclusion: Non carriers of the allele A385 of FAAH showed an improvement on insulin and HOMA-R levels with a high protein hypocaloric diet after weight loss during 9 months. A standard hypocaloric diet produced a similar improvement in lipid profile in both genotypes.