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

Abstract

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 ¼ 419, M ¼ 237, F ¼ 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 ¼ normal, 26.7-28.4 ¼ overweight, 31.6-49.7 ¼ 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 w 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 ¼ 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.

Polymorphisms in the endocannabinoid receptor 1 in relation to fat mass distribution

“…In a Belgian cohort, the CNR1 rs1049353 SNP was found to be associated with waist-to-hip ratio (WHR) in obese men (10). Likewise, in a study from Southern Italy (11), rs1049353 was linked with obesity; however, neither of these results were confirmed in studies on obese German children and adolescents (12) or mid-age American adults in the Framingham Study (13).…”

Are endocannabinoid type 1 receptor gene (CNR1) polymorphisms associated with obesity and metabolic syndrome in postmenopausal Polish women?

“…Many investigators have suggested than an association exists between various CNR1 gene polymorphisms and the parameters of obesity in various populations. [8][9][10]16,17 On the other hand, Lieb et al, 18 who studied 18 singlenucleotide polymorphisms in the CNR1 gene in 2415 Framingham Offspring Study participants, found no evidence for an association of CNR1 polymorphisms with BMI, waist circumference, or visceral or subcutaneous adipose tissue.…”

Endocannabinoid-Mediated Control of Synaptic Transmission

“…A number of genetic polymorphisms have been described in the CB 1 receptor, and their correlation with various conditions has been examined (386). Although the results are rather controversial, some of the polymorphisms have been reported to link to obesity-related phe-notypes (173,448), hebephrenic schizophrenia (78,530), childhood attention deficit/hyperactivity disorder (429), and depression in Parkinson's disease (20).…”