title: Circulating Endocannabinoids and the Polymorphism 385C>A in Fatty Acid Amide Hydrolase (FAAH) Gene May Identify the Obesity Phenotype Related to Cardiometabolic Risk: A Study Conducted in a Brazilian Population of Complex Interethnic Admixture.
abstract: The dysregulation of the endocannabinoid system is associated with cardiometabolic complications of obesity. Allelic variants in coding genes for this system components may contribute to differences in the susceptibility to obesity and related health hazards. These data have mostly been shown in Caucasian populations and in severely obese individuals. We investigated a multiethnic Brazilian population to study the relationships among the polymorphism 385C>A in an endocannabinoid degrading enzyme gene (FAAH), endocannabinoid levels and markers of cardiometabolic risk. Fasting plasma levels of endocannabinoids and congeners (anandamide, 2-arachidonoylglycerol, N-oleoylethanolamide and N-palmitoylethanolamide) were measured by liquid chromatography-mass spectrometry in 200 apparently healthy individuals of both genders with body mass indices from 22.5 ± 1.8 to 35.9 ± 5.5 kg/m2 (mean ± 1 SD) and ages between 18 and 60 years. All were evaluated for anthropometric parameters, blood pressure, metabolic variables, homeostatic model assessment of insulin resistance (HOMA-IR), adiponectin, leptin, C-reactive protein, and genotyping. The endocannabinoid levels increased as a function of obesity and insulin resistance. The homozygous genotype AA was associated with higher levels of anandamide and lower levels of adiponectin versus wild homozygous CC and heterozygotes combined. The levels of anandamide were independent and positively associated with the genotype AA position 385 of FAAH, C-reactive protein levels and body mass index. Our findings provide evidence for an endocannabinoid-related phenotype that may be identified by the combination of circulating anandamide levels with genotyping of the FAAH 385C>A; this phenotype is not exclusive to mono-ethnoracial populations nor to individuals with severe obesity.
authors.affiliation: Laboratory of Clinical and Experimental Pathophysiology (CLINEX), Rio de Janeiro State University (UERJ), Rio de Janeiro, RJ, Brazil.
authors.forename: Cyro José de Moraes
authors.initials: CJ
authors.lastname: Martins
authors.affiliation: Laboratory of Clinical and Experimental Pathophysiology (CLINEX), Rio de Janeiro State University (UERJ), Rio de Janeiro, RJ, Brazil.|Pro-Rector for Research and Postgraduate Education, UNIGRANRIO, Duque de Caxias, RJ, Brazil.
authors.forename: Virginia
authors.initials: V
authors.lastname: Genelhu
authors.affiliation: Genetics Department, Rio de Janeiro State University (UERJ), Rio de Janeiro, RJ, Brazil.
authors.forename: Marcia Mattos Gonçalves
authors.initials: MM
authors.lastname: Pimentel
authors.affiliation: Laboratory of Clinical and Experimental Pathophysiology (CLINEX), Rio de Janeiro State University (UERJ), Rio de Janeiro, RJ, Brazil.
authors.forename: Bruno Miguel Jorge
authors.initials: BM
authors.lastname: Celoria
authors.affiliation: Laboratory of Clinical and Experimental Pathophysiology (CLINEX), Rio de Janeiro State University (UERJ), Rio de Janeiro, RJ, Brazil.
authors.forename: Rogerio Fabris
authors.initials: RF
authors.lastname: Mangia
authors.affiliation: Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli NA, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Aveta
authors.affiliation: Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli NA, Italy.
authors.forename: Cristoforo
authors.initials: C
authors.lastname: Silvestri
authors.affiliation: Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli NA, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
authors.affiliation: Laboratory of Clinical and Experimental Pathophysiology (CLINEX), Rio de Janeiro State University (UERJ), Rio de Janeiro, RJ, Brazil.|Pro-Rector for Research and Postgraduate Education, UNIGRANRIO, Duque de Caxias, RJ, Brazil.
authors.forename: Emilio Antonio
authors.initials: EA
authors.lastname: Francischetti
mesh_terms: D052242:Adiponectin / Q000097:blood; D000328:Adult; D000577:Amides; D000581:Amidohydrolases / Q000235:genetics*; D000886:Anthropometry; D001095:Arachidonic Acids / Q000097:blood; D001794:Blood Pressure; D015992:Body Mass Index; D001938:Brazil; D063388:Endocannabinoids / Q000097:blood*; D004983:Ethanolamines / Q000097:blood; D005006:Ethnicity; D005260:Female; D005838:Genotype; D005989:Glycerides / Q000097:blood; D006706:Homeostasis; D006720:Homozygote; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000208:ethnology* / Q000235:genetics*; D009829:Oleic Acids / Q000097:blood; D010169:Palmitic Acids / Q000097:blood; D010641:Phenotype; D011110:Polymorphism, Genetic; D053284:Polyunsaturated Alkamides / Q000097:blood; D015995:Prevalence; D012307:Risk Factors; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D052242:Adiponectin; D000577:Amides; D000581:Amidohydrolases; D001095:Arachidonic Acids; D063388:Endocannabinoids; D004983:Ethanolamines; D005989:Glycerides; D009829:Oleic Acids; D010169:Palmitic Acids; D053284:Polyunsaturated Alkamides; D000099252:Fatty Acid Amide Hydrolases; C488250:oleoylethanolamide; C005958:palmidrol; C094503:glyceryl 2-arachidonate; C078814:anandamide