Are there any risks associated with comt gene polymorphism in the presence of cannabis?

Course of study: Biochemistry

Student name: Jana Kasperova

Student number: 1030022

Date: 06/05/2014

Supervisor name: Dr Winston Morgan

Abstract

Cannabis is widespread illicit drug used by people worldwide. Documentary evidence determined 50 % of the psychotic disorders to be associated with cannabis use. Psychoactive molecule delta-9-tetrahydrocannabinol exerts its effects via endocannabinoid system. The cannabinoid receptors are abundant throughout the brain, therefore known to have an association with neuropsychiatric disturbances. Complex disorders such as schizophrenia come from combined interaction of genetic and environmental factors. Several studies have placed the catechol-o-methyltransferase (COMT) gene as good candidate for schizophrenia. The efficiency of cortical function is controlled by COMT gene polymorphism, which is involved in catabolism of dopamine in prefrontal cortex. The objective of the present study was to examine if genetic variation in the COMT moderated THC-induced effects on psychotic symptoms among patients with schizophrenia and healthy individuals. Several single nucleotide polymorphisms were examined in order to understand susceptibility genes for schizophrenia. The finding displayed the effect of adolescent cannabis use on adult psychosis to be mediated by genetic variation in the COMT gene. Among the high degree of linkage disequilibrium between SNPs rs737865 and rs165688, it was suggested that the effect of Val156Met polymorphism on schizophrenia is due to SNP rs737865. These findings have important implications for understanding the effects of cannabis use and COMT on psychotic disorders. It would be of interest to investigate several gene and gene interactions between COMT and other genes to understand of how the effects of such genes affecting liability to psychosis in the presence of environmental risk factors.

Contents

Are there any risks associated with COMT gene polymorphism in the presence of cannabis? 0

Abstract 1

Introduction 4

Tetrahydrocannabinol 5

Endogenous ligands 8

Gene variations of CNR1 and CNR2 in neuropsychiatric disorders 9

GxE interactions 9

COMT polymorphism is a mediator of the link between cannabis and psychosis. 11

Aims 14

Materials and Methods 15

Results 17

The effect of adolescent cannabis use on adult psychosis is controlled by genetic variation in the COMT gene. 17

Determination of allele frequencies by DNA pooling and LD between SNPs 21

Determination of genetic association with schizophrenia by employing individual genotyping 22

Association analysis at individual SNPs 23

Linkage disequilibrium analysis 26

Common haplotype analysis 26

COMT rs4680 in relation to psychotic experiences 28

Discussion 31

Conclusion 35

References 36

Abstract 1

Introduction 3

Tetrahydrocannabinol 3

Endogenous ligands 5

Gene variations of CNR1 and CNR2 in neuropsychiatric disorders 6

GxE interactions 6

COMT polymorphism is a mediator of the link between cannabis and psychosis. 8

Aims 11

Materials and Methods 12

Results 13

The effect of adolescent cannabis use on adult psychosis is controlled by genetic variation in the COMT gene. 13

Determination of allele frequencies by DNA pooling and LD between SNPs 16

Determination of genetic association with schizophrenia by employing individual genotyping 17

Association analysis at individual SNPs 18

Linkage disequilibrium analysis 21

Common haplotype analysis 21

COMT rs4680 in relation to psychotic experiences 23

Discussion 25

Conclusion 28

References 30