The G1422A variant of the cannabinoid receptor gene (CNR1) is associated with abdominal adiposity in obese men

Since recent data suggest that the endocannabinoid system controls food intake through central, and lipogenesis via peripheral CB1 receptors, we hypothesized that genetic variation at the cannabinoid receptor-1 (CNR1) locus could have an effect on adiposity. We investigated, whether a specific CNR1 G1422A genotype is associated with anthropometric markers of obesity and fat distribution in adult obese individuals. A total of 1,064 obese subjects (BMI > or = 30 kg/m2) without diabetes, impaired glucose tolerance or other endocrine diseases and 251 healthy control persons were genotyped for the G1422A variant (rs1049353) with a TaqMan assay. Anthropometric measures as body weight, BMI, waist and waist-to-hip ratio (WHR) were assessed by classical methods. Fat mass (FM) was measured by bio-impedance. The prevalence of the G1422A variant was not significantly different between cases and controls (OR = 1.056; P = 0.626). In obese women, no meaningful associations between CNR1 genotype and anthropometric parameters were found. In obese men, CNR1 1422 A/A genotype was significantly associated with higher WHR (P = 0.009) and waist circumference (P = 0.008) after adjusting for age and BMI. Fat mass percentage showed an association (P = 0.011) which disappeared after adjusting for age and BMI. A trend for an association was seen for fat mass (unadjusted P = 0.099; adjusted P = 0.033). Our data indicate that the G1422A polymorphism in the CNR1 gene is associated with increased abdominal adiposity in obese men.