Association between cannabinoid type-1 receptor polymorphism and body mass index in a southern Italian population

Context: Endocannabinoids control food intake via both central and peripheral mechanisms, and cannabinoid type-1 receptor (CB1) modulates lipogenesis in primary adipocyte cell cultures and in animal models of obesity. Objectives: We aimed to evaluate, at the population level, the frequency of a genetic polymorphism of CB1 and to study its correlation with body mass index. Design, setting and participants: Healthy subjects from a population survey carried out in southern Italy examined in 1992-1993 and older than 65 years (n=419, M=237, F=182) were divided into quintiles by body mass index (BMI). Two hundred and ten subjects were randomly sampled from the first, third and fifth quintile of BMI (BMI, respectively: 16.2-23.8=normal, 26.7-28.4=overweight, 31.6-49.7=obese) to reach a total of 70 per quintile. Their serum and white cells from the biological bank were used to measure the genotype and the blood variables for the study. Measurements: Anthropometric parameters, blood pressure, serum glucose and lipid levels were measured with standard methods; genotyping for the CB1 1359G/A polymorphism was performed using multiplex PCR. Statistical methods included χ ² for trend, binomial and multinomial multiple logistic regression to model BMI on the genotype, controlling for potential confounders. Results: We found a clear trend of increasing relative frequency of the CB1 wild-type genotype with the increase of BMI (P=0.03) and, using a multiple logistic regression model, wild-type genotype, female gender, age, glycaemia and triglycerides were directly associated with both overweight (third quintile of BMI) and obesity (fifth quintile of BMI). Conclusions: Although performed in a limited number of subjects, our results show that the presence of the CB1 polymorphic allele was significantly associated with a lower BMI.