Association of genetic variation in cannabinoid mechanisms and gastric motor functions and satiation in overweight and obesity

Background The endocannabinoid system is associated with food intake. We hypothesized that genes regulating cannabinoids are associated with obesity. Genetic variations in fatty acid amide hydroxylase (FAAH) and cannabinoid receptor 1 (CNR1) are associated with satiation and gastric motor function. Methods In 62 overweight or obese adults of European ancestry, single nucleotide polymorphisms of rs806378 (nearest gene CNR1) and rs324420 (nearest gene FAAH) were genotyped and the associations with gastric emptying (GE) of solids and liquids, gastric volume (GV), and satiation [maximum tolerated volume (MTV) and symptoms after Ensure ^® nutrient drink test] were explored using a dominant genetic model, with gender and BMI as covariates. Key Results rs806378 CC genotype was associated with reduced fasting GV (210.2±11.0mL for CC group compared to 242.5±11.3mL for CT/TT group, P=0.031) and a modest, non-significant association with GE of solids (P=0.17). rs324420 genotype was not associated with alterations in gastric motor functions; however, there was a difference in the Ensure ^® MTV (1174.6±37.2mL for CC group compared to 1395.0±123.1mL for CA/AA group, P=0.046) suggesting higher satiation with CC genotype. Conclusions & Inferences Our data suggest that CNR1 and FAAH are associated with altered gastric functions or satiation that may predispose to obesity.