(AAT)n repeat in the cannabinoid receptor gene, CNR1: association with schizophrenia in a Spanish population

The cannabinoid receptor 1 gene (CNR1) has been associated with addictive disorders and schizophrenia in different studies. We have compared the frequencies of the alleles for the 3'-UTR CNR1 microsatellite in a sample of 113 Spanish schizophrenic patients, including 68 with comorbid substance abuse, and 111 healthy controls. We report that the frequency of the allele 4 of this microsatellite is significantly lower in schizophrenia patients when compared with controls (chi(2) = 7.858; df 1; P = 0.005). No differences have been found with respect to substance abuse.Thus, the allele 4 represents, in our sample, a protective factor against schizophrenia (odds ratio 0.468, 95% confidence interval (CI) 0.27-0.79). The population attributable genetic risk for the allele 4 absence is 30% (95% CI = 17-41%) and the attributable risk for the allele 4 absence in those with schizophrenia is 53% (95% CI = 20-73%). Our results suggest that, independent of substance abuse, differences in the cannabinoid system function could be involved in the vulnerability to schizophrenia in Spanish population.