Effects of C358A missense polymorphism of the endocannabinoid degrading enzyme fatty acid amide hydrolase on weight loss after a hypocaloric diet

• Published in: Metabolism, clinical and experimental clinical and experimental, 2011-05, Vol.60 (5), p.730-734
• Main Authors: de Luis, Daniel Antonio, Gonzalez Sagrado, Manuel, Aller, Rocio, Izaola, Olatz, Conde, Rosa
• Format: Article
• Language: English
• Subjects: Adult; Amidohydrolases - genetics; Blood glucose; Blood Glucose - genetics; Blood Glucose - metabolism; Blood pressure; Blood Pressure - genetics; Body Composition - genetics; Body mass; Body Mass Index; Caloric Restriction; Cannabinoid Receptor Modulators - metabolism; Cholesterol - blood; Cholesterol - genetics; Cholesterol, LDL - blood; Diet (effects); Diet (weight control); Endocannabinoids; Endocrinology & Metabolism; Female; Humans; Lipids; Male; Middle Aged; Mutation, Missense; Obesity; Obesity - blood; Obesity - diet therapy; Obesity - genetics; Polymorphism, Genetic; Prospective Studies; Waist; Waist Circumference - genetics; Weight control; Weight Loss - genetics
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/j.metabol.2010.07.007

Abstract The Pro129THr, C385A, polymorphism of FAAH gene (rs324420C>A) has been associated with overweight and obesity. We investigate the role of this polymorphism on anthropometric and metabolic responses to a weight loss program. Obese individuals (n = 122) were assessed at baseline and after 3 months of a hypocaloric diet. There were 76.2% (n = 93) homozygotes for the C allele, 23.8% (n = 27) AC heterozygotes, and 1.6% (n = 2) homozygotes for the A allele. After the dietary intervention, all individuals decreased their body weight (in kilograms), body mass index (in kilograms per square meter), fat mass (in kilograms), waist circumference (in centimeters), and systolic blood pressure (in millimeters of mercury). In mutant-type group, the decrease in weight was 3.5 ± 3.6 kg (decrease in wild-type group, 2.4 ± 3.8 kg); and the decrease in waist circumference was 5.4 ± 6.4 cm (decrease in wild-type group, 2.6 ± 4.8 cm). Individuals with the A/C or AA genotype had a significant reduction ( P < .05) in glucose (96.5 ± 12.5 vs 92.3 ± 10.5 mg/dL; difference, 2.68 ± 1.81 mg/dL), total cholesterol (215.3 ± 49 vs 193.3 ± 27.6 mg/dL; difference, 14.31 ± 7.21 mg/dL), and low-density lipoprotein cholesterol (133.6 ± 53 vs 106.7 ± 39.2 mg/dL; difference, 15.87 ± 9.61 mg/dL) levels. The A allele at rs324420 in the FAAH gene was associated with larger improvements in glucose, total cholesterol, low-density lipoprotein cholesterol, body mass, and waist circumference after a dietary intervention.