Author:

Abstract:

Background: Metabolic disturbances are more prevalent in patients with schizophreniathan in the general population. The endocannabinoid system plays an important role in the regulation of dopamine transmission and several metabolic pathways, and the endocannabinoid receptor type 1 gene (CNR1) is considered a candidate gene for both schizophrenia and metabolic disorders. We examined whether genetic variation in CNR1 was associated with metabolic syndrome (MetS) in a naturalistic cohort of 407 patients with schizophrenia. Methods: A total of 7 identified tag SNPs in CNR1, located in the 5’ region (rs6454674), intron 2 (rs806377, rs1535255, rs806379 and rs6928499), exon 3 (rs2023239) and exon 4 (rs1049353), were genotyped. Presence of MetS was assessed using the adapted ATP-III criteria. All the statistical analyses were performed using STATA 11.0. Associations were considered statistically significant at p<0.007 (0.05/7) using Bonferroni correction. Results: The minor alleles of rs6928499, rs1535255 and rs2023239 were nominally associated with a lower risk of MetS (OR: 0.56, 95%C.I.: 0.37-0.84, p=0.006, OR: 0.56, 95%C.I.: 0.37-0.84, p=0.006, and OR: 0.44, 95%C.I.: 0.27-0.72, p=0.001, respectively, adjusted for age, gender, duration of illness, clozapine or olanzapine treatment). These differences were mainly due to differences in high-density lipoprotein cholesteroland fasting glucose, but not in body mass index (BMI) or waist circumference. No significant association of the other polymorphisms (rs806377, rs1049353, rs6454674, and rs806379) with MetS was found. Moreover either BMI as a continuous variable or BMI ≥ 30 was not associated with any SNPs. Conclusion: The results provide evidence that the prevalence of MetS is associated with the CNR1 gene in patients with schizophrenia during long-term treatment with antipsychotic treatment. Further studies are needed to uncover the exact molecular basis for this association, which could provide novel treatment targets for the MetS.