title: Endocannabinoid Pro129Thr FAAH functional polymorphism but not 1359G/A CNR1 polymorphism is associated with antipsychotic-induced weight gain.
abstract: Several candidate genes have been associated with antipsychotic-induced body weight (BW) gain. Because the endocannabinoid system is deeply involved in BW regulation, endocannabinoid genes may have a role in the antipsychotic-induced weight gain. Therefore, we investigated the 1359 G/A (rs1049353) single nucleotide polymorphisms (SNP) of the cannabinoid receptor 1 (CNR1) gene, which codes the endocannabinoid CB1 receptor, and the complementary DNA (cDNA) 385C/A (rs324420) SNP of the FAAH gene, which codes the endocannabinoid degrading enzyme, for their role in BW changes induced by antipsychotic drugs. Eighty-three white psychotic patients who underwent a naturalistic treatment with different antipsychotics (clozapine, olanzapine, risperidone, quetiapine, and haloperidol) and completed a 24-week treatment period were included into the study together with 80 age- and sex-matched white healthy controls. At the 24th week of treatment, 41 patients gained more than 7% of their baseline BW. No significant differences between patients and controls emerged in genotype and allele frequencies of both SNPs. Genotype and allele frequencies of the FAAH cDNA 385C/A SNP but not of the CNR1 1359 G/A SNP significantly differed between subjects who gained more than 7% of BW and those who did not, with both AC and AA genotypes and the A allele being significantly more frequent in patients who gained more than 7% of their baseline BW. Present findings, although obtained in a small population and in a naturalistic setting, suggest that the cDNA 385C/A SNP of the FAAH gene may predispose subjects to get a clinically meaningful weight gain after antipsychotic exposure.
authors.affiliation: Department of Psychiatry, University of Naples SUN, Naples, Italy. monteri@tin.it
authors.forename: Palmiero
authors.initials: P
authors.lastname: Monteleone
authors.forename: Walter
authors.initials: W
authors.lastname: Milano
authors.forename: Claudio
authors.initials: C
authors.lastname: Petrella
authors.forename: Benedetta
authors.initials: B
authors.lastname: Canestrelli
authors.forename: Mario
authors.initials: M
authors.lastname: Maj
mesh_terms: D000328:Adult; D000483:Alleles; D000581:Amidohydrolases / Q000235:genetics*; D014150:Antipsychotic Agents / Q000009:adverse effects*; D016022:Case-Control Studies; D018076:DNA, Complementary / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics*; D015430:Weight Gain / Q000187:drug effects* / Q000235:genetics; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D014150:Antipsychotic Agents; D018076:DNA, Complementary; D043884:Receptor, Cannabinoid, CB1; D000099252:Fatty Acid Amide Hydrolases