Genetic Polymorphisms of the Endocannabinoid System in Obesity and Diabetes.

The endocannabinoid system (ECS) is involved in many physiological processes including fertility, pain and energy regulation. The aim of this systematic review was to examine the contribution of single nucleotide polymorphisms (SNPs) of the ECS to adiposity and glucose metabolism. Database searches returned 734 articles, of which 65 were included covering 70 SNPs in genes coding for cannabinoid receptors 1 and 2 (CB₁ , CB₂ ), fatty acid amide hydrolase (FAAH) and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD). No studies included SNPs relating to monoacylglycerol lipase or diacylglycerol lipase. The CB₁ receptor SNP rs1049353 showed 17 associations with lower body mass index (BMI) and fat mass (5 studies). It also showed 3 associations with lower insulin levels (1 study). Conversely, the CB₁ receptor SNP rs806368 was associated with increased BMI and waist circumference (2 studies). The FAAH SNP rs324420 as associated with increased obesity (3 studies). A haplotype of NAPE-PLD was associated with decreased BMI (1 study). 60 SNPs showed no association with any measured outcome. This review suggests a complex but important role of ECS SNPs in energy and glucose metabolism. This article is protected by copyright. All rights reserved.