Variability in the COMT gene and modification of the risk of schizophrenia conferred by cannabis consumption

Abstract

Introduction: The risk of schizophrenia conferred by cannabis has recently been proposed to be modulated by the Val158Met polymorphism (rs4680) at the COMT gene. To date, these findings have not been replicated in independent samples.

Material and methods: We tested the potential gene-by-environment interaction between Val158Met genotype at the COMT gene and previous use of cannabis in schizophrenia in 192 healthy controls and 91 inpatients with DSM-IV schizophrenia. The functional COMT Val158Met polymorphism was analyzed using TaqMan technology. Cannabis use was measured by taking into account the frequency of intake during the previous month. Logistic regression models were used to test the interaction between genetic and environment factors.

Results: Cannabis use was strongly associated with the case condition (p<0.0001). The Val158Met polymorphism at the COMT gene was not associated with schizophrenia, although Val/Val homozygosity tended to be more frequent in the case group than in the control group (34% vs 27%; OR=1.39; 95% CI, 0.78-2.47). Finally, in women we found a non-significant trend toward the association when we tested for the interaction between cannabis use, the number of Val alleles and susceptibility to schizophrenia (p=0.152).

Conclusions: Our results tend to support recent findings suggesting that the Val158Met polymorphism at the COMT gene modifies the risk of schizophrenia conferred by cannabis use. In our study, this possible effect was only detected in women.