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

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.

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.

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.

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 chi2 for trend, binomial and multinomial multiple logistic regression to model BMI on the genotype, controlling for potential confounders.

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).

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.